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Cardiac CT, Coronary CT Angiography, Calcium Scoring and CT Fractional Flow Reserv... of 80

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Cardiac CT, Coronary CT Angiography, Calcium Scoringand CT Fractional Flow Reserve

Policy History

Last Review

05/02/2019

Effective: 04/09/1998

Next

Review: 02/27/2020

Review History

Definitions

Additional Information

Clinical Policy Bulletin

Notes

Number: 0228

Policy *Please see amendment for Pennsylvania Medicaid at the end of this CPB.

I. Aetna considers cardiac computed tomography (CT)

angiography of the coronary arteries using 64-slice or

greater medically necessary for the following

indications:

A. Rule out obstructive coronary stenosis in

symptomatic persons with a low or intermediate pre

test probability of coronary artery disease or

atherosclerotic cardiovascular disease by

Framingham risk scoring, Pooled Cohort

Equations, or by American College of Cardiology

(ACC) criteria (see Appendix),

B. Rule out obstructive coronary stenosis in persons

with a low or intermediate pre-test probability of

coronary artery disease or atherosclerotic

cardiovascular disease by Framingham risk scoring,

Pooled Cohort Equations, or by American College of

Cardiology (ACC) criteria (see Appendix) with a Proprietary

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positive (i.e., greater than or equal to 1 mm ST

segment depression) stress test.

C. Evaluation of asymptomatic persons at an

intermediate pre-test probability of coronary heart

disease or atherosclerotic cardiovascular disease by

Framingham risk scoring or Pooled Cohort

Equations (see Appendix) who have an equivocal or

uninterpretable exercise or pharmacological stress

test or have resting electrocardiogram (ECG) changes

(such as left bundle branch block (LBBB), pathologic q-

waves, or right bundle branch block (RBBB) with left

anterior fascicular block (LAFB) in which coronary

artery disease (CAD) is a possible etiology. Note :

Current guidelines from the American Heart

Association recommend against routine stress

testing for screening asymptomatic adults.

D. Pre-operative assessment of persons scheduled to

undergo 'high-risk" non-cardiac surgery, where an

imaging stress test or invasive coronary angiography

is being deferred unless absolutely necessary.

The ACC defines high-risk surgery as emergent

operations, especially in the elderly, aortic and other

major vascular surgeries, peripheral vascular

surgeries, and anticipated prolonged surgical

procedures with large fluid shifts and/or blood loss

involving the abdomen and thorax.

E. Pre-operative assessment for planned non-coronary

cardiac surgeries including valvular heart disease,

congenital heart disease, and pericardial disease, in

lieu of cardiac catheterilzation as the initial imaging

study, in persons with low or intermediate pretest

risk of obstructive CAD.

F. Detection and delineation of suspected coronary

anomalies in young persons (less than 30 years of

age) with suggestive symptoms (e.g., angina,

syncope, arrhythmia, and exertional dyspnea

without other known etiology of these symptoms in

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children and adults; dyspnea, tachypnea, wheezing,

periods of pallor, irritability (episodic crying),

diaphoresis, poor feeding and failure to thrive in

infants).

G. Calculation of fractional flow reserve (HeartFlow

FFRCT) for persons who have a coronary CTA that has

shown coronary artery disease of uncertain

functional significance, or is non-diagnostic.

II. Aetna considers CT angiography of cardiac morphology

for pulmonary vein mapping medically necessary for the

following indications:

A. Evaluation of persons needing biventricular

pacemakers to accurately identify the coronary veins

for lead placement.

B. Evaluation of the pulmonary veins in persons

undergoing pulmonary vein isolation procedures for

atrial fibrillation (pre- and post-ablation procedure).

III. Aetna considers CT angiography medically necessary

for preoperative assessment of the aortic valve annulus

prior to anticipated transcatheter aortic valve

replacement (TAVR).

IV. Aetna considers cardiac computed tomography (CT)

angiography medically necessary for evaluation of aortic

erosion in symptomatic members (e.g., chest pain) who

have been treated for atrial septal defect with an

occlusive device.

V. Aetna considers cardiac CT for evaluating cardiac

structure and morphology medically necessary for the

following indications:

A. Anomalous pulmonary venous drainage;

B. Evaluation of other complex congenital heart

diseases;

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C. Evaluation of sinus venosum atrial-septal defect;

D. Kawasaki's disease;

E. Person scheduled or being evaluated for surgical

repair of tetralogy of Fallot or other congenital heart

diseases;

F. Pulmonary outflow tract obstruction;

G. Suspected or known Marfan's syndrome;

H. Evaluation of suspected native or prosthetic cardiac

valve dysfunction when echocardiographic imaging is

inconclusive or there is suspicion for paravalvular

abscess formation.

VI. Aetna considers cardiac CT angiography experimental

and investigational for persons with any of the following

contraindications to the procedure because its

effectiveness for indications other than the ones listed

above has not been established:

A. Body mass index (BMI) greater than 40 (except when

3rd generation Dual-Source CT (DSCT) 120-kv tube

voltage is utilized).

B. Inability to image at desired heart rate (under 80

beats/min), despite beta blocker administration.

C. Person with allergy or intolerance to iodinated

contrast material

D. Persons in atrial fibrillation (except when rate-

controlled and 3rd generation Dual-Source CT (DSCT)

120-kv tube voltage is utilized).or with other

significant arrhythmia.

E. Persons with extensive coronary calcification by plain

film or with prior Agatston score greater than 1000.

Aetna considers cardiac CT angiography using less than 64-slice

scanners experimental and investigational because the

effectiveness of this approach has not been established.

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VII. Aetna considers coronary CT angiography experimental

and investigational for screening of asymptomatic

persons, evaluation of atherosclerotic burden,

evaluation of persons at high pre-test probability of

coronary artery disease, evaluation of stent occlusion or

in-stent restenosis, evaluation of persons with an

equivocal PET rubidium study, identification

of vulnerable plaques, monitoring of atheroma burden,

and for all other indications (e.g., atrial

angiosarcoma) because its effectiveness for these

indications has not been established. Note: The

selection of CT angiography should be made within the

context of other testing modalities such as stress

myocardial perfusion images or cardiac ultrasound

results so that the resulting information facilitates the

management decision and does not merely add a new

layer of testing.

VIII. Aetna considers a single calcium scoring by means of

low-dose multi-slice CT angiography, ultrafast [electron

beam] CT, or spiral [helical] CT medically necessary

for screening the following: (i) asymptomatic persons

age 40 years and older with diabetes; or (ii)

asymptomatic persons with an intermediate (10 % to 20

%) 10-year risk of cardiac events based on Framingham

Risk Scoring or Pooled Cohort Equations (see Appendix).

Repeat calcium scoring is considered medically

necessary only if the following criteria are met: (i)

member’s most recent coronary artery calcium (CAC)

scan result was zero, (ii) member's most recent CAC

scan was at least 5 years ago, and (iii) discovery of

coronary calcium would change management.

Otherwise, serial or repeat calcium scoring is considered

experimental and investigational.

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Aetna considers calcium scoring by means of low-dose CT

angiography medically necessary for persons who meet criteria

for diagnostic cardiac CT angiography to assess whether an

adequate image of the coronary arteries can be obtained.

Aetna considers calcium scoring of the aortic valve medically

necessary in the setting of persons with suspected paradoxical

low-flow, low-gradient symptomatic severe aortic stenosis when

transthoracic echocardiography is inconclusive.

IX. Aetna considers coronary CT angiography experimental

and investigational for assessment of coronary

atherosclerosis in asymptomatic diabetics who do not

otherwise meet the above criteria for CT coronary

angiography because of insufficient evidence.

X. Aetna considers calcium scoring (e.g., with ultrafast

[electron-beam] CT, spiral [helical] CT, and multi-slice

CT) experimental and investigational for all other

indications because of insufficient evidence in the peer-

reviewed published medical literature.

Background

Cardiac CT Angiography

Coronary computed tomography angiography (CCTA) is a

noninvasive imaging modality designed to be an alternative to

invasive cardiac angiography (cardiac catheterization) for

diagnosing CAD by visualizing the blood flow in arterial and

venous vessels. The gold standard for diagnosing coronary

artery stenosis is cardiac catheterization.

Contrast-enhanced cardiac CT angiography (CTA) involves

the use of multi-slice CT and intravenously administered

contrast material to obtain detailed images of the blood

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vessels of the heart. Beta-blockers and sublingual nitrates may

be administered prior to the scan in order to lower the heart

rate, avoid arrhythmia and dilate the coronary arteries. In order

to allow for an improved image quality and contrast media

dose reduction, the CCTA is usually ECG-triggered to adapt

the scan sequence to the person's heartbeat (Bell et al., 2018).

In addition to being a non-invasive alternative to conventional

invasive coronary angiography for evaluating coronary artery

disease, CCTA has emerged as the gold-standard for the

detection of coronary artery anomalies Ramjattan and

Makaryus, 2018).

The performance of cardiac CTA has been improved by

increasing the number of slices that can be acquired

simultaneously by increasing the number of detector rows

(AHTA, 2006). As the number of slices that can be acquired

simultaneously increases, the scan time is shortened, spatial

resolution is increased, and reconstruction artifacts are

significantly reduced. Initial cardiac CT imaging was

conducted with 4-slice detector CT. Scanning times were

reduced from 40 seconds down to 20 seconds with 16-slice

detector CT. With the advent of 64-slice detector CT, scanning

times were reduced to a 10 second breath-hold. Current

generation scanners can perform full volumetric acquisition

requiring only 1 cardiac cycle (1 R-R interval) and/or can be

performed without breath holding (Abbara et al, 2016).

Cardiac CTA using 64-slices has been shown in studies to

have a high negative predictive value (93 to 100 %), using

conventional coronary angiography as the reference standard.

Given its high negative predictive value, cardiac CTA has been

shown to be most useful for evaluating persons at low to

intermediate risk of coronary artery disease. This would

include evaluation of asymptomatic low- to intermediate-risk

persons with an equivocal exercise or pharmacologic stress

test, and evaluation of low- to intermediate-risk persons with

chest pain. Cardiac CTA is also a useful alternative to invasive

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coronary angiography for pre-operative evaluation of persons

undergoing non-coronary cardiac surgery or high-risk non-

cardiac surgery, where invasive coronary angiography would

otherwise be indicated.

Einstein and colleagues (2007) ascertained the lifetime

attributable risk (LAR) of cancer incidence associated with

radiation exposure from a 64-slice computed tomography

coronary angiography (CTCA) study and evaluated the

influence of age, sex, and scan protocol on cancer risk. Organ

doses from 64-slice CTCA to standardized phantom

(computational model) male and female patients were

estimated using Monte Carlo simulation methods, using

standard spiral CT protocols. Age- and sex-specific LARs of

individual cancers were estimated using the approach of BEIR

VII and summed to obtain whole-body LARs. Main outcome

measures were whole-body and organ LARs of cancer

incidence. Organ doses ranged from 42 to 91 mSv for the

lungs and 50 to 80 mSv for the female breast. Lifetime cancer

risk estimates for standard cardiac scans varied from 1 in 143

for a 20-year old woman to 1 in 3,261 for an 80-year old man.

Use of simulated electrocardiographically controlled tube

current modulation (ECTCM) decreased these risk estimates

to 1 in 219 and 1 in 5,017, respectively. Estimated cancer

risks using ECTCM for a 60-year old woman and a 60-year old

man were 1 in 715 and 1 in 1911, respectively. A combined

scan of the heart and aorta had higher LARs, up to 1 in 114 for

a 20-year old woman. The highest organ LARs were for lung

cancer and, in younger women, breast cancer. The authors

concluded that these estimates derived from simulation

models suggested that use of 64-slice CTCA is associated

with a non-negligible LAR of cancer. This risk varies markedly

and is considerably greater for women, younger patients, and

for combined cardiac and aortic scans.

Arbab-Zadeh et al (2012) evaluated the impact of patient

population characteristics on accuracy by CTA to detect

obstructive CAD. For the CORE-64 (Coronary Artery

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Evaluation Using 64-Row Multidetector Computed

Tomography Angiography) study, a total of 371 patients

underwent CTA and cardiac catheterization for the detection of

obstructive CAD, defined as greater than or equal to 50 %

luminal stenosis by quantitative coronary angiography (QCA).

This analysis includes 80 initially excluded patients with a

calcium score greater than or equal to 600. Area under the

receiver-operating characteristic curve (AUC) was used to

evaluate CTA diagnostic accuracy compared to QCA in

patients according to calcium score and pre-test probability of

CAD. Analysis of patient-based quantitative CTA accuracy

revealed an AUC of 0.93 (95 % CI: 0.90 to 0.95). The AUC

remained 0.93 (95 % CI: 0.90 to 0.96) after excluding patients

with known CAD but decreased to 0.81 (95 % CI: 0.71 to 0.89)

in patients with calcium score greater than or equal to 600 (p =

0.077). While AUCs were similar (0.93, 0.92, and 0.93,

respectively) for patients with intermediate, high pre-test

probability for CAD, and known CAD, negative predictive

values were different: 0.90, 0.83, and 0.50, respectively.

Negative predictive values decreased from 0.93 to 0.75 for

patients with calcium score les than 100 or greater than or

equal to 100, respectively (p = 0.053). The authors concluded

that both pre-test probability for CAD and coronary calcium

scoring should be considered before using CTA for excluding

obstructive CAD. For that purpose, CTA is less effective in

patients with calcium score greater than or equal to 600 and in

patients with a high pre-test probability for obstructive CAD.

(CTA is most useful as a rule-out test in patients with low-

intermediate pre-test probability of disease and mild coronary

calcification or those with a calcium score of zero".

The use of 64-slice CCTA scanners was associated with a non-

negligible effective radiation dose and thus, may increase the

lifetime attributable risk of cancer. However, second-

generation CCTA scanners may be used which can decrease

the amount of radiation exposure. A study by Chen and

colleagues (2013) reported on 107 participants who received

CCTA with a second-generation 320-detector row machine

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Cardiac CT, Coronary CT Angiography, Calcium Scoring and CT Fractional Flow Res... of 80

and compared the radiation exposure to 100 participants who

had previous imaging with a first-generation scanner. For the

second-generation scanner the median radiation dose was

0.93 mSv and 2.76 mSv with the first-generation scanner. This

radiation dose places CT scans at an intermediate (1–10 mSv)

level of risk under international guidelines, a risk level for

which the corresponding benefit should be "moderate" to

"substantial." Einstein and colleagues (2007) reported that the

use of a 64-slice CCTA is associated with a non-negligible

LAR (lifetime attributable risk) of cancer and that the risk is

"Considerably greater for women, younger patients and for

combined cardiac and aortic scans." CCTA requires the use of

intravenous iodinated contrast and, in most cases, beta-

blocker or calcium channel blocker medications to slow the

heart rate prior to image acquisition. In patients with a GFR >

60, the risks for nephrotoxicity are very low (<1%). Beta-

blocker and calcium channel blocker administration,

particularly given the short duration of use, are associated with

a very low risk (<1%) for adverse reactions. Additionally,

CCTA may offer an option in obese patients as data suggests

no significant reduction in sensitivity and specificity when

compared to non-obese patients. Particularly on newer CT

scanner platforms, diagnostic quality images are expected

even in patients with modest HR control prior to acquisition,

though more thorough pre-scan HR control does allow for

better radiation dose reduction. Limitations to utilization of

CCTA include patients with irregular heart rhythms, known

high levels of coronary calcification (CAC scores > 400),

borderline tachycardia (HR>80 despite pre-treatment),

baseline renal impairment, and known IV contrast allergy.

A number of controlled clinical trials and registry evidence

have addressed the diagnostic accuracy and clinical

effectiveness of CCTA in the evaluation of symptomatic

patients. Registry data can be broadly subdivided into those

that address the use of CCTA to evaluate individuals with

symptoms suggestive of CAD, to risk stratify individuals at risk

for coronary artery disease, and those that use CCTA after

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equivocal results of other cardiac imaging procedures, such as

myocardial perfusion imaging (MPI) or echocardiography. In

part these proposed uses result from the observation that a

negative CCTA has high negative predictive value for the

presence of CAD (Bluemke, 2008).

There is a large body of evidence evaluating the diagnostic

characteristics of CCTA for identifying coronary lesions. The

best estimate of the diagnostic characteristics of CCTA can be

obtained from recent meta-analyses and systematic reviews.

Sensitivities for functional stress testing tended to range

between 70% and 90%, depending on t he test and study, and

specificities ranged between 70% and 90%. For CCTA,

estimates of sensitivity from various systematic reviews are

considerably higher. The guideline statement from Fihn cited

studies reporting sensitivities between 93% and 97%. A meta-

analysis by Ollendorf et al. of 42 studies showed a summary

sensitivity estimate of 98% and a specificity of 85%. A meta-

analysis of 8 studies conducted by the Ontario Health Ministry

showed a summary sensitivity estimate of 97.7% and a

specificity of 79%. In the meta-analysis by Nielsen et al.,

sensitivity of CCTA varied between 98% and 99% (depending

on the analysis group). The biggest criticism of historical trials

investigating the diagnostic characteristics of any non-invasive

testing modality is referral bias: only patients with abnormal

tests were referred for invasive coronary angiography (ICA).

The recently published P ICTURE trial is a prospective,

multicenter investigation enr olling 230 patients with chest pain

referred for MPI who were subsequently randomized to CCTA

or MPI. All patients were then referred for ICA regardless of

noninvasive test findings. In this trial, the sensitivity of CCTA to

predict a stenosis >50% on ICA was far superior to MPI

utilizing both a CCTA stenosis ≥50% (92.0% vs 54.5%,

p<0.001) or ≥70% (92.6% vs 59.3%, p<0.001). The odds ratio

for CAD on ICA was 12.73 (95%CI 2.43-66.55, p<0.001) for a

summed stress score by MPI ≥5% (utilizing a 17-segment

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model). In contrast, the odds ratio for CAD on ICA was 51.75

(95% CI 8.50-314.94, p<0.001) for CCTA utilizing a stenosis

≥50% (Ollendorf et al, 2011).

The extent and severity of CAD by CCTA has significant

prognostic implications. Long term follow-up data from the

CONFIRM registry observed that the absence of CAD on

CCTA is associated with very favorable prognosis with major

adverse cardiac event rates (MACE) of < 1% out to 7 years.

This “warranty period” affords the ability to avoid future

unnecessary ischemic testing and provide r eassurance to

patients. Lin et al found 2.09% mortality rate at 3 years of follow-

up in over 2,500 symptomatic patients with nonobstructive CAD

(HR 1.98 (1.06-3.69), p=0.03). Up to 25% of nonobstructive

CAD (<50%) patients and 50% of obstructive CAD (≥50%)

patients will not have detectable perfusion def ects by single-

photon emission c omputed tomography (SPECT), thus a

significant cohort of these patients at significant risk for

mortality and cardiovascular events would be underdiagnosed

and incorrectly risk stratified. CCTA provided incremental

prognostic information after adjusting for traditional risk factors

with hazard ratios of 2.20 and 2.91 in the 2-vessel and 3-vessel

groups, respectively (p=0.013 and 0.001) (Lin et al, 2011).

In addition to very robust diagnostic and prognostic

performance when compared to invasive coronary

angiography, there is now considerable prospective

randomized data demonstrating that CCTA meaningfully

guides provider decision making, resulting in improved patient

outcomes. SCOT-HEART is a randomized, prospective trial of

more than 4,000 patients being evaluated for stable chest

pain. Following initial clinical evaluation and, in 85% of

patients, an exercise stress electrocardiogram, patients were

assigned to undergo CCTA or continue with their previously

determined plan of care. A diagnosis of coronary heart

disease was made in 47% of participants and 36% of patients

were labeled as having angina due to coronary heart disease

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following initial clinical evaluation. At 6 weeks, CCTA

reclassified 558 (27%) patients to a diagnosis of CHD and 481

(23%) patients to a diagnosis of angina due to CHD (standard

care 22 [1%] and 23 [1%]; p<0·0001). CCTA increased the

provider diagnostic certainty, as well as the frequency of the

diagnosis of CHD (RR 2.56, 95% CI 2·33–2·79; p<0·0001 and

RR 1·09, 95% CI 1·02–1·17; p=0·0172, respectively).

Furthermore, CCTA also increased provider certainty in the

diagnosis of angina due to CHD (RR 1·79, 95% CI 1·62–1·96;

p<0·0001). This reclassification and increase in diagnostic

certainty resulted in an increased rate of change in planned

investigation (15% vs 1%; p<0·0001) and in medical

treatments (23% vs 5%; p<0·0001) following CCTA. While

there was no significant difference in outcomes reported at 1.7

years of follow-up in the initial publication, 3 year follow-up

data showed a significant reduction in both fatal and non-fatal

myocardial infarction. A similar reduction in non-fatal MI was

observed in the prospective, multicenter PROMISE trial, which

randomized over 10,000 intermediate pre-test risk patients

with stable chest pain symptoms to a strategy of functional

testing or CCTA as the initial diagnostic evaluation. While

PROMISE was a neutral trial with no difference in the primary

endpoint between the CCTA arm (3.3%) and the functional-

testing arm (3.0%, adjusted HR 1.04; 95% CI 0.83-1.29,

p=0.75), death and non-fatal MI was less frequent in the CCTA

arm at 12 months of follow-up (HR 0.66, p=0.049).

Additionally, a recently published investigation of the

PROMISE data demonstrated superior prognostic and

discriminatory ability with CCTA compared with functional

testing, in addition to an improvement in appropriate initiation

of primary prevention medications, such as aspirin (11.8% vs

7.8%), statins (12.7% vs 6.2%), and beta blockers (8.1% vs

5.3%, p<0.0001 for all) in patients in the CCTA arm when

compared to functional testing. The prevalence of healthy

eating (p=0.002) and lower rates of obesity (p=0.040) were

also observed following C CTA when compared to functional

testing (SCOT-HEART investigators, 2015).

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A recent meta-analysis combining data from PROMISE and

SCOT-HEART, in addition to a 3rd prospective randomized

stable chest pain trial (CAPP), concluded that CCTA was

associated with a 31% reduction in non-fatal myocardial

infarction (HR 0.69, 95% CI 0.49-0.98, p=0.038). While not

included in this meta-analysis, recently published data from

the nationwide Danish registry demonstrated that evaluation of

stable chest pain with CCTA was associated with greater use

of statins and aspirin, likely explaining the observed reduction

in non-fatal MI in this cohort. CCTA was, however, associated

with higher rates of ICA and functional testing costs (Williams

et al, 2017).

This observed improvement in hard cardiovascular outcomes

following CCTA is likely explained by the unique ability of

CCTA to not only detect significant epicardial coronary vessel

stenosis, but also to diagnose non-obstructive coronary

atherosclerosis. This early detection of CAD allows for early,

aggressive implementation of primary prevention medications

and positively impacts patient adoption and adherence to

lifestyle modifications regarding diet, exercise, smoking

cessation, and weight loss. Data in 2,800 consecutive

symptomatic patients undergoing CCTA at tertiary hospital

centers suggested that CAD burden, even in the absence of a

severe stenosis by CCTA, resulted in intensification of primary

prevention medical therapy by providers. Additionally, in

patients with nonobstructive CAD, those treated with statin

therapy had a mortality reduction compared to those without

atherosclerotic plaque on CCTA. CCTA also identified a high

risk cohort of patients with extensive nonobstructive CAD in

whom statin therapy was associated with a significant

reduction in cardiovascular death and non-fatal MI (HR=0.18,

p=0.011) (Hulten et al, 2014).

Data from the National Cardiovascular Data Registry’s (NCDR)

CathPCI Registry demonstrated that, despite a multitude of

noninvasive testing modalities available to providers

nationwide, 58.4% of patients were found to have no or

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nonobstructive CAD at the time of elective ICA. In contrast,

only 30% of patients referred for ICA after CCTA were found to

have nonobstructive CAD. Revascularization based on

findings of high-risk CAD on CCTA was associated with a

significant reduction in all-cause mortality with

revascularization when compared to medical therapy alone

(2.3% vs 5.3%, p=0.008) in the CONFIRM registry.

Additionally, the opposite effect was observed in patients

without high-risk CAD referred for revascularization compared

with medical therapy (2.3% vs 1.0%, p=0.0138). The CCTA

allows for more precise risk stratification beyond simple

epicardial stenosis for appropriately selecting patients who

benefit from revascularization. In prospective trials, CCTA was

associated with increased rates of revascularization. A meta-

analysis by Hulten et al looking at CCTA in the ED for acute

chest pain patients demonstrated a cost savings in 3 of the 4

large randomized control trials (RCTs) and shorter hospital

lengths of stay in all 4 studies. An increased referral rate for

ICA (OR 1.36, 95% CI 1.03-1.80, p=0.030) and subsequent

revascularization (OR 1.81, 95% CI 1.20-2.72, p=0.004) was

also observed with a number needed to scan to increase ICA

and revascularization ov er usual care by 1 of 48 and 50,

respectively. The strategy of CCTA as a “gatekeeper” to the

catheterization lab was recently presented in soon to be

published data from the CONSERVE trial. This multicenter,

prospective trial enrolled stable chest pain patients without

known CAD who were referred for ICA. Patients were

randomized to undergo CCTA followed by selective

catheterization based on CCTA results (and at the discretion

of the provider) or direct catheterization in patients with

elective indications for diagnostic coronary angiography. Pre-

test risk, rates of abnormal non-invasive stress testing, and

symptoms were similar between the groups. CCTA followed by

selective catheterization was associated w ith a 78% reduction

(p<0.001) in per-patient testing, which included the index

evaluation plus downstream costs, when compared with direct

catheterization. Revascularization rates were 41% lower

(p<0.001) in the selective catheterization arm, as well. This

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resulted in a 50% cardiovascular cost savings ($3,338 vs

$6,740, p<0.001) utilizing CCTA as a gatekeeper. Importantly,

MACE outcomes were the same between the two strategies

over study follow-up. In summary, CCTA can appropriately

identify patients who would most benefit from referral for ICA

and revascularization and result in lower rates of normal or

minimally abnormal findings on ICA making CCTA an effective

gatekeeper to the catheterization laboratory. The use of CCTA

does seem to increase the rates of revascularization when

compared to functional testing, both in the stable chest pain

and ED population (Hulten, 2017).

The addition of CCTA early in the evaluation of patients

presenting acutely to the emergency department with chest

pain has been extensively studied in prospective, multicenter

trials. A 2012 randomized trial by Hoffman and colleagues

(ROMICAT II) compared the effectiveness of CCTA with that of

standard evaluation in individuals suggestive of acute coronary

syndrome in the emergency room. A total of 501 individuals

had CCTA, 499 individuals had a standard evaluation in the

emergency room. Individuals were excluded if they had

known CAD. The primary endpoint of length of hospital stay

was significantly reduced in the CCTA cohort. Additionally, the

a priori secondary effectiveness endpoint of time to diagnosis

was also decreased with CCTA. Of note, there was more

downstream testing and radiation exposure was higher in the

CCTA cohort.In another randomized trial, Litt et al (2012)

compared individuals at low-to-intermediate risk with possible

acute coronary syndromes who presented to the emergency

room. Individuals were randomly assigned in a 2:1 ratio to

undergo CCTA or receive traditional care. The primary

outcome was safety (measured by the rate of cardiac events

within 30 days). None of the participants with a negative CCTA

had myocardial infarction or died within 30 days. There were

no cardiac deaths in the traditional group. And while the CCTA

group had a higher rate of discharge from the emergency

room and decreased overall length of stay, there were no

differences between t he groups in the use of invasive

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angiography or rate of revascularization. The CT-STAT trial

(Goldstein et al) compared CCTA with MPI in the early

evaluation of nearly 700 patients with acute chest pain and

found a 54% reduction in time to diagnosis (p<0.0001), a 38%

reduction in cost of care (p<0.0001), and no difference in

MACE rates. A subsequentmeta-analysis by Hulten et al

concluded that ED CCTA was associated with decreased cost

and reduced length of stay, but increased ICA and

revascularization rates. In summary, the high negative

predictive value (NPV) of CCTA in patients presenting to the

ED with chest pain permits ruling out coronary disease with

high accuracy. The efficiency of the workup is improved,

because patients are safely and quickly discharged from the

ED with no adverse outcomes among patients with negative

CCTA examinations. Finally, CCTA was associated with

improved clinical outcomes when instituted in the immediate

post-discharge evaluation of patients with acute chest pain

discharged from the ED as reported in the CATCH trial. CCTA

demonstrated lower rates of a composite of cardiac death, MI,

unstable angina, late symptom-driven revascularization, and

chest pain readmission when compared to standard care

utilizing bicycle exercise ECG or MPI (11% vs 16%, p=0.04;

HR 0.62, 95% CI 0.40-0.98). Additionally, when looking only at

major adverse cardiovascular events (MACE), a CCTA-guided

strategy was also superior (2% vs 5%, p=0.04), predominantly

driven by higher rates of myocardial infarction in the standard

care cohort. CCTA was also compared to high-sensitivity

troponin assays (hs-troponins) in the evaluation and

disposition of acute chest pain patients presenting to the ED.

In a prospective, multicenter trial of 500 patients randomized

to hs-troponin based evaluation and disposition to CCTA,

there was no difference in the primary endpoint of patients

identified with significant CAD requiring revascularization.

Additionally, ED discharge rates, ED length of stay, and

incidence of undetected ACS were similar. CCTA lowered

direct medical costs by 34% (p<0.01) when compared to hs-

troponins and there was less downstream testing following the

index ED visit (4% vs 10%, p<0.01).

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An assessment by the Blue Cross Blue Shield Association

Technology Evaluation Center's Evidence Street (revised June

2017) concluded that CCTA in individuals with stable chest

pain and intermediate risk for CAD, the evidence is sufficient to

determine that the technology results in a meaningful

improvement in the net health outcome for patients.

Additionally, prior assessment found that CCTA was equally

powerful in patients with acute chest pain presenting to the

emergency room with no known history of coronary artery

disease, and found not to have evidence of acute coronary

syndromes. The TEC assessment stated that evidence

obtained in the emergency setting, similar to more extensive

results among ambulatory patients, indicates a normal CCTA

appears to provide a prognosis as good as other noninvasive

tests (BCBSA, 2011).

Cardiac CT angiography often produces non-cardiac incidental

findings. To evaluate the incidence, clinical importance, and

costs of these incidental findings, MacHaalany, et al

(2009) studied 966 consecutive patients who underwent CTA.

Incidental findings were noted in 401 patients (41.5 %); of

these, 12 were deemed to be clinically significant (e.g., 5

thrombi, 1 aortic dissection that was not clinically suspected, 1

ruptured breast implant), and 68 were deemed to be

indeterminate (e.g., 34 non-calcified pulmonary nodules less

than 1 cm, 11 larger lung nodules, 9 liver nodules/cysts). After

a mean 18-month follow-up, no indeterminate finding became

clinically significant, although 3 malignancies were diagnosed

after subsequent diagnostic tests. Non-cardiac and cancer

death rates were not significantly different between patients

with and without incidental findings. In all, 164 additional

diagnostic tests and procedures were performed in the 80

patients with indeterminate or clinically significant incidental

findings, including 1 patient who suffered empyema and

abdominal abscesses as a complication of transthoracic

biopsy.

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In an observational study,Kim and colleagues (2013)

evaluated the prevalence and characteristics of coronary

atherosclerosis in asymptomatic subjects classified as low-risk

by National Cholesterol Education Program (NCEP) guideline

using CCTA. A total of 2,133 (49.2 %) subjects, who were

classified as low-risk by the NCEP guideline, of 4,339

consecutive middle-aged asymptomatic subjects who

underwent CCTA with 64-slice scanners as part of a general

health evaluation were included in this study. Main outcome

measures were the incidence of atherosclerosis plaques and

significant stenosis. In the subjects at low-risk, 11.4 % (243 of

2,133) of subjects had atherosclerosis plaques, 1.3 % (28 of

2,133) of subjects had significant stenosis, and 0.8 % (18 of

2,133) of subjects had significant stenosis caused by non-

calcified plaque (NCP). Especially, 75.0 % (21 of 28) of

subjects with significant stenosis and 94.4 % (17 of 18) of

subjects with significant stenosis caused by NCP were young

adults. Mid-term follow-up (29.3 ± 14.9 months) revealed 4

subjects with cardiac events: 3 subjects with unstable angina

requiring hospital stay and 1 subject with percutaneous

coronary intervention. The authors concluded that although an

asymptomatic population classified as low-risk by the NCEP

guideline has been regarded as a minimal risk group, the

prevalence of atherosclerosis plaques and significant stenosis

were not negligible. However, considering very low event rate

for those patients, CCTA should not be performed in low-risk

asymptomatic subjects, although CCTA might have the

potential for identification of high-risk groups in the selected

subjects regarded as a minimal-risk group by NCEP guideline.

Dorr and associates (2013) stated that clinical studies have

consistently shown that there is only a very weak correlation

between the angiographically determined severity of CAD and

disturbance of regional coronary perfusion. On the other

hand, the results of randomized trials with a fractional flow

reserve (FFR)-guided coronary intervention (DEFER, FAME I,

FAME II) showed that it is not the angiographically determined

morphological severity of CAD but the functional severity

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determined by FFR that is critical for prognosis and the

indications for re-vascularization. A non-invasive method

combining the morphological image of the coronary anatomy

with functional imaging of myocardial ischemia is therefore

particularly desirable. An obvious solution is the combination

of CCTA with a functional procedure, such as perfusion

positron emission tomography (PET), perfusion single photon

emission computed tomography (SPECT) or perfusion

magnetic resonance imaging (MRI). This can be performed

with fusion imaging or with hybrid imaging using PET-CT or

SPECT-CT. First trial results with PET-CCTA and SPECT-

CCTA carried out as cardiac hybrid imaging on a 64-slice CT

showed a major effect to be a decrease in the number of false-

positive results, significantly increasing the specificity of CCTA

and SPECT. The authors concluded that although the results

are promising, due to the previously high costs, low availability

and the additional radiation exposure, current data are not yet

sufficient to give clear recommendations for the use of hybrid

imaging in patients with a low-to-intermediate risk of CAD.

Moreover, they stated that ongoing prospective studies such

as the SPARC or EVINCI trials will bring further clarification.

In a retrospective study, Kang et al (2014) evaluated coronary

arterial lesions and assessed their correlation w ith clinical

findings in patients with Takayasu arteritis (TA) by using

coronary CT angiography. A total of 111 consecutive patients

with TA (97 females, 14 males; mean age of 44 years ± 13.8

[standard deviation]; age range of 14 to 74 years) underwent

CT angiography of the coronary arteries and aorta with 128-

section dual-source CT. Computed t omography angiographic,

clinical, and laboratory findings of each patient were

retrospectively reviewed. Statistical differences between

coronary CT angiographic findings and clinical parameters

were examined with uni-variate analysis. Of 111 patients, 32

(28.8 %) had cardiac symptoms and the remaining 79 (71.2 %)

had no cardiac symptoms; 59 patients (53.2 %) had coronary

arterial lesions at coronary CT angiography. Three main

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radiologic features were detected: (i) coronary ostial stenosis

(n = 31, 28.0 %), (ii) non-ostial coronary arterial stenosis (n =

41, 36.9 %), and (iii) coronary aneurysm (n = 9, 8.1 %).

Coronary artery ostial or luminal stenosis of 50 % or more or

coronary aneurysms were observed in 26 (23.4 %) patients

with TA. Patients with coronary arterial abnormalities at

coronary CT angiography had higher incidences of

hypertension (p = 0.02), were older at the time of CT (p =

0.01), and had longer duration of TA (p = 0.02) than those

without coronary artery abnormalities. The presence of

cardiac symptoms, disease activity, and other co-morbidities

was not associated with differences in coronary artery

involvement. The authors concluded that in patients with TA,

there is a high prevalence of coronary arterial abnormalities at

coronary CT angiography, regardless of disease activity or

symptoms. Thus, these researchers noted that coronary CT

angiography may add information on coronary artery lesions in

patients with TA.

Marwick et al. (2015) discussed the potential of CCTA to serve

as an effective gatekeeper to invasive coronary angiography.

The authors note that functional testing prior to ICA is not

widespread. Possibly as a consequence, 40% of angiograms

in the National Cardiovascular Database Registry detect

normal coronary arteries. The authors reviewed the PROMISE

trial outcomes and noted that although the findings are

insufficient to conclude the possibility of either harm or benefit

from the use of CCTA, a particularly salient feature was that

although catheterization was performed in more CCTA

patients in the 90 days following noninvasive testing, the

likelihood of nonsignificant CAD was significantly lower in the

CCTA group (3.4% vs. 4.3%; p = 0.02). The authors state that

CCTA is a promising noninvasive method for identification and

exclusion of CAD, which may provide a diagnostic paradigm to

curb unnecessary invasive testing. CCTA has the potential to

serve as an effective gatekeeper to curb unnecessary ICA.

However, there is no definitive evidence to favor either a

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CCTA-guided or a stress testing–guided approach for

evaluation of acute CP. The authors believe the PROMISE trial

results are equivocal and concluded that results from future

prospective multicenter studies will be needed to justify

CCTA’s contribution to patients with suspected CAD for ICA.

Williams et al. (2016) conducted a prospective, randomized,

controlled, multicenter trial to evaluate the consequences of

CCTA-assisted diagnosis on invasive coronary angiography

(ICA), preventive treatments, and clinical outcomes. A little

over 4,000 patients were randomized to receive standard care

or standard care plus coronary computed tomography

angiography (CCTA). The investigators found that despite

similar overall rates (409 vs. 401; p = 0.451), ICA was less

likely to demonstrate normal coronary arteries (p < 0.001) but

more likely to show obstructive CAD (p = 0.005) in those

allocated to CCTA. More preventive therapies (p < 0.001) were

initiated after CCTA, with each drug commencing at a median

of 48 to 52 days after clinic attendance. From the median time

for preventive therapy initiation (50 days), fatal and nonfatal

myocardial infarction was halved in patients allocated to CCTA

compared with those assigned to standard care (p = 0.020).

Cumulative 6-month costs were slightly higher with CCTA:

difference $462 (95% CI: $303 to $621). The investigators

concluded that their findings show that CCTA allows m ore

appropriate and effective selection of ICA related to CAD.

CCTA is generally contraindicated for decompensated heart

failure; however, may be considered on a case-by-case basis

(Abbara et al, 2016).

Jorgensen et al. (2017) conducted an observational, non-

randomized study to compare functional testing to CCTA in

patients with stable coronary artery disease. The investigators

studied patients enrolled in a Danish registry who underwent

initial noninvasive cardiac testing with either a CCTA or

functional testing (exercise electrocardiography or nuclear

stress testing) from 2009 to 2015. They further evaluated the

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use of noninvasive testing, invasive procedures, medications,

and medical costs within 120 days. Out of 86,705 patients,

53,744 underwent functional testing and 32,961

underwent CCTA. Compared with functional testing, there was

significantly higher use of statins (15.9% vs. 9.1%), aspirin

(12.7% vs. 8.5%), invasive coronary angiography (14.7% vs.

10.1%), and percutaneous coronary intervention (3.8% vs.

2.1%); all p < 0.001 after CCTA. The mean costs of

subsequent testing, invasive procedures, and medications

were higher after CCTA (p < 0.001). Unadjusted rates of

mortality (2.1% vs. 4.0%) and MI hospitalization (0.8% vs.

1.5%) were lower after CCTA than functional testing (both p <

0.001). After adjustment, CCTA was associated with a

comparable all-cause mortality (HR: 0.96; 95% CI: 0.88 to

1.05), and a lower risk of MI (HR: 0.71; 95% CI: 0.61 to 0.82).

The investigators concluded that CCTA was associated with

greater use of statins, aspirin, invasive procedures, and higher

costs than functional testing in stable patients who were

evaluated for suspected CAD. The investigators also

concluded that although CCTA was associated with a lower

risk of MI, it had a similar risk of all-cause mortality.

The Prospective Multicenter Imaging Study for Evaluation of

chest pain (PROMISE) trial was a pragmatic trial that recruited

a large cohort from USA and Canadian centres to determine

whether an initial assessment of suspected stable CAD using

CTCA reduces major adverse cardiovascular events (Douglas,

et al., 2015). There was no improvement in death, myocardial

infarction or major procedural complication after a median of

2-years of follow-up when compared with a functional-guided

strategy.

Hoffman et al. (2017) discussed insights from the prospective,

randomized, multicenter PROMISE trial which evaluated the

prognostic value of noninvasive cardiovascular testing in

patients with stable chest pain. The authors note that there are

limited data from randomized trials comparing anatomic with

functional testing for determining optimal management of

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patients with stable chest pain. In the PROMISE trial, patients

with stable chest pain and intermediate pretest probability for

obstructive CAD were randomly assigned to functional testing

(exercise electrocardiography, nuclear stress, or stress

echocardiography) or CCTA. The primary end point was death,

myocardial infarction, or unstable angina hospitalizations over

a median follow-up of 26.1 months. Both the prevalence of

normal test results and incidence rate of events in these

patients were significantly lower among 4500 patients

randomly assigned to CTA in comparison with 4602 patients

randomly assigned to functional testing (both P<0.001). In

CTA, 54.0% of events (n=74/137) occurred in patients with non-

obstructive CAD (1%-69% stenosis). Prevalence of obstructive

CAD and myocardial ischemia was low (11.9% versus 12.7%,

respectively), with both findings having s imilar prognostic value

(95% CI, 2.60-5.39; and 3.47; 95% CI,

2.42-4.99). When test findings were stratified as mildly,

moderately, or severely abnormal, hazard ratios for events in

comparison w ith normal tests increased proportionally for CTA

(2.94, 7.67, 10.13; all p<0.001) but not for corresponding

functional testing categories (0.94 [p=0.87], 2.65 [p=0.001],

3.88 [p<0.001]). They found that anatomic assessment

with CCTA provided significantly better prognostic information

compared to function testing (p=0.04). They noted that adding

the Framingham Risk Score to functional test results

significantly improved the prognostic value of functional

testing. If 2714 patients with at least an intermediate

Framingham Risk Score (>10%) who had a normal functional

test were reclassified as being mildly abnormal, the

discriminatory capacity improved to 0.69 (95% CI, 0.64-0.74).

The authors stated that contemporary stable chest pain

populations present with a low prevalence of myocardial

ischemia and obstructive CAD, and that in that particular

population, CCTA provides better prognostic information than

functional testing. The authors concluded that in this

population, the detection of non-obstructive CAD identifies

additional at-risk patients while consideration of the

Framingham Risk Score is important for proper risk

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stratification of patients with normal stress testing. These

results may contribute to a better understanding of how to use

this information to guide management of these patients.

Newer generation CT scanners have emerged which al lows

for faster, higher-quality images. Dual-Source CT (DSCT)

scanners allow for a "gapless acquisition with a pitch of up to

3.4 which cannot be achieved with conventional single-source

CT scanners. A high-pitch spiral acquisition can be performed

in less than one second and thus information from a single

heartbeat can be generated. In combination with iterative

reconstruction techniques, high-pitch spiral acquisition allows

for cardiac CT with sub-milliSievert doses". Contraindications

include acute MI, screening asymptomatic patients with low-to-

intermediate risk of CAD, evaluation of coronary artery stents

less than 3 mm, and evaluation of asymptomatic patients post

CABG less than 5 years old and post sent placement less than

2 years old (Bell et al., 2018).

CCTA with slower temporal resolution scanners, such as the

64-slice single-source CT scanner, is not recommended in

persons with significant arrhythmia or atrial fibrillation (AF).

Arrhythmias have presented a challenge due to motion artifact

resulting from irregular rhythm; however, studies are now

showing that newer generation CT scanners are capable of

providing quality images for patients with AF. CCTA with dual-

source CT scanner technology and algorithms have been

developed to perform CCTA in persons with atrial fibrillation

who cannot be effectively imaged with single-source CT.

These newer generation CT scanners allow faster temporal

resolution and are capable of producing motion-free images

(Soman et al, 2017).

Yang et al. (2015) evaluated 85 patients with persistent atrial

fibrillation (AF) who underwent prospective ECG-triggered

sequential second-generation dual-source CCTA. Their aim

was to evaluate the effects of mean heart rate (HR) and heart

rate variation (HRV) on image quality and analyze the

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diagnostic accuracy. Tube current and voltage were adjusted

according to BMI (range 17.3-36.3 kg/m 2) and iterative

reconstruction was used. Image quality of coronary segments

(four-point scale) and presence of significant stenosis (>50%)

were evaluated. Diagnostic accuracy was analyzed in 30 of

the 85 patients who underwent additional invasive coronary

angiography (ICA). All subjects had AF longer than 1 year.

The results showed that 8 of 1102 (0.7%) segments

demonstrated poor image qua lity. No significant impact on

image quality was found f or mean HR (p=0.663) or HRV

(p=0.895). On per-segment analysis, sensitivity, specificity,

positive predictive value (PPV), and negative predictive value

(NPV) were 89.7% (26/29), 99.4% (355/357), 92.9% (26/28),

and 99.2% (355/358), respectively, with excellent correlation

(kappa=0.91) with ICA. Mean effective dose was 3.3±1.0 mSv.

The authors concluded that "prospectively ECG-triggered

sequential dual-source CCTA provides diagnostic image

quality and good diagnostic accuracy for detection of coronary

artery stenosis in AF patients without significant influence by

HR or HRV."

The Society of Cardiovascular Computed Tomography (SCCT)

guidelines committee produced an update in 2016 which

states that "the developmentof dual-source CT and wide-

detector scanners may allow imaging of selected patients with

higher and irregular heart rates such as atrial fibrillation with

diagnostic imaging quality. It should be acknowledged,

however that coronary CTA in high or irregular heart rates

typically is associated with a higher radiation dose. Moreover,

in the event of irregular heart rates or atrial fibrillation it is

essential that other determinants of imagequality such as

coronary calcification, body weight and patient cooperation are

taken into consideration before deciding whether to proceed

with the scan. The presence of frequent premature complexes

prior to scanning therefore should trigger consideration of

aborting the examination." (Abbara et al, 2016).

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Prazeres et al. (2018) compared image quality and radiation

dose of coronary computed tomography (CT) angiography

performed with dual-source CT scanner using 2 different

protocols in patients with atrial fibrillation (AF). The study

included 732 subjects with AF who underwent 2 different

acquisition protocols: double high-pitch (DHP) spiral

acquisition and retrospective spiral acquisition. The image

quality was ranked according to a qualitative score by 2

experts: 1, no evident motion; 2, minimal motion not

influencing coronary artery luminal evaluation; and 3, motion

with impaired luminal evaluation. A third expert was included

to resolve any disagreement. The results reflected that the

DHP group (24 patients, 374 segments) showed more

segments classified as score 1 than the retrospective spiral

acquisition group (71.3% vs 37.4%). Image quality evaluation

agreement was high between observers (κ = 0.8). There was

significantly lower radiation exposure for the DHP group (3.65

[1.29] vs 23.57 [10.32] mSv). The authors concluded that their

comparison s howed that a double high-pitch spiral protocol for

CCTA acquisition resulted in lower radiation exposure and

superior image quality in patients with AF compared with

conventional spiral retrospective acquisition.

With the advent of the 3rd generation dual-source CT, persons

with BMI greater than or equal to 40 may now be able to

undergo a CCTA. Mangold et al. (2016) conducted a

retrospective study to evaluate the quality of 3rd generation

dual-source CT (CCTA) in obese patients. The study included

102 obese patients who had undergone CCTA performed with

(3rd) generation dual-source CT, prospectively ECG-triggered

acquisition at 120 kV, and automated tube current modulation.

Patients were divided into three BMI groups: (i) 25-29.9 kg/m

(2); (ii) 30-39.9 kg/m 2); and (iii) ≥ 40 kg/m(2). Vascular

attenuation in the coronary arteries was measured. Contrast-

to-noise ratio (CNR) was calculated. Image quality was

subjectively evaluated using five-point scales. Image quality

was considered diagnostic in 97.6 % of examinations. CNR

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was consistently adequate in all groups but decreased for

groups 2 and 3 in comparison to group 1 as well as for group 3

compared to group 2 (p = 0.001, respectively). Subjective

image quality was significantly higher in group 1 compared to

group 3 (p < 0.001). The mean effective dose was 9.5 ± 3.9

mSv for group 1, 11.4 ± 4.7 mSv for group 2 and 14.0 ± 6.4

mSv for group 3. The authors concluded that diagnostic CCTA,

with 3(rd) generation DSCT at 120 kV, can routinely be

performed in persons with BMI greater than 40.

Chinnaiyan et al. (2009) investigated the dual-source

computed tomography (DSCT), which was novel at that time,

in morbidly obese patients. The authors state that persons with

BMI greater than or equal to 40 have an increased risk of

cardiovascular morbidity and mortality but have not been able

to obtain a CCTA due to reduced accuracy. The authors

conducted an observational study of 50 patients with mean

BMI 44.8. Each patient served as their own control. After a

single DSCT acquisition, standard quarter-scan image

reconstructions at a temporal resolution of 83 milliseconds

were compared with temporal resolution reconstructions at

105, 125, and 165 milliseconds. Images were evaluated for

diagnostic adequacy score and for image noise, signal-to-

noise ratio, and contrast-to-noise ratio. In each patient, the

image reconstruction with the best visual diagnostic score was

compared with the control image for quantitative measures.

The authors found that scans were of diagnostic quality in 47

(94%) patients using the "best reconstruction" compared wi th

38 (76%) patients using quarter-scan reconstruction.

Significant improvements were observed in noise (p < 0.0001),

contrast-to-noise ratio (p = 0.0038), and signal-to-noise ratio (p

= 0.030). The authors concluded that "CCTA with DSCT using

a modified scan protocol and adjustable temporal

reconstructions provides diagnostic image quality in >90% of

morbidly obese patients."

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A 2016 guideline update produced by the Society of

Cardiovascular Computed Tomography (SCCT) discussed

weight considerations for CCTA. The guidelines states that

"scan settings should be adjusted to the patient's body weight.

Both tube voltage and tube current should be optimized to

deliver the least necessary radiation for adequate image

quality. In obese patients, higher tube current and tube voltage

are required in order to preserve contrast to noise ratio. More

importantly, tube current should be adjusted to the total

volume of soft tissues within the scanned region. The specific

adjustments are dependent on the scanner specifications

(Abbara et al., 2016).

Noninvasive Fractional Flow Reserve (HeartFlow FFRCT)

HeartFlow FFRCT (HeartFlow, Inc, Redwood City, CA) is a

coronary physiologic simulation software used for the clinical

qualitative and quantitative analysis of previously acquired

computerized tomography Digital Imaging and

Communications in Medicine (DICOM) data. The software

provides a non-invasive method of estimating fractional flow

reserve using standard coronary CT angiography (CCTA)

image data (NICE, 2017).

FFR is the ratio between the maximum blood flow in a

narrowed artery and the maximum blood flow in a normal

artery. FFR is currently measured invasively using a pressure

wire placed across a narrowed artery. An assessment by the

BlueCross BlueShield Association Technology Evaluation

Center (BCBSA, 2011) concluded that invasive fractional flow

reserve guideded percutaneous coronary intervention (PCI)

results in better outcomes than an angiography alone guided

strategy for persons who are undergoing revascularization.

The assessment concluded that "The evidence is consistent

with prior physiologic data and long-held beliefs that identifying

stenoses is insufficient to determine when revascularization is

likely to have benefit. If revascularization is anticipated in

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patients with angina, evidence supports a conclusion that

FFR-guided PCI results in better outcomes than an

angiography alone-guided strategy."

A medical consultation technology document from the National

Institute for Health and Care Excellence (NICE, 2016) found

that "[t]he case for adopting HeartFlow FFRCT for estimating

fractional flow reserve from coronary CT (CCT) angiography is

supported by the evidence. The technology is non-invasive

and safe, and has a high level of diagnostic accuracy." The

consultation stated that HeartFlow FFRCT should be

considered as an option for patients with stable, recent onset

chest pain of suspected cardiac origin and a clinically

determined intermediate (10% to 90%) risk of coronary artery

disease. The consultation technology document found that,

using HeartFlow FFRCT may avoid the need for invasive

coronary angiography and revascularisation. For correct use,

HeartFlow FFRCT requires access to 64-slice (or above)

coronary CT angiography facilities.

NICE guidance (2017) states that "[t]he case for adopting

HeartFlow FFRCT for estimating fractional flow reserve from

coronary CT angiography (CCTA) is supported by the

evidence........ HeartFlow FFRCT should be considered as an

option for patients with stable, recent onset chest pain who are

offered CCTA as part of the NICE pathway on chest pain.

Using HeartFlow FFRCT may avoid the need for invasive

coronary angiography and revascularisation." The guidance

notes that, for correct use, HeartFlow FFRCT requires access

to 64-slice (or above) CCTA facilities. Because the safety and

effectiveness of FFRCT analysis has not been evaluated in

other patient subgroups, HeartFlow FFRCT is not

recommended in patients who have an acute coronary

syndrome or have had a coronary stent, coronary bypass

surgery or myocardial infarction in the past month.

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The American College of Cardiology CathPCI Registry

(Messenger, et al., 2017) has announced that they will allow

FFRCT as an acceptable noninvasive method of documenting

ischemia around the time of revascularization. Documentation

of ischemia around the time of revascularization is important to

the appropriate use criteria (AUC) for percutaneous coronary

interventions (PCI).

Calcium Scoring

Coronary artery calcium (CAC) scoring is a noninvasive test

that has been reported to detect the presence of subclinical

coronary artery disease (CAD) by measuring the location and

extent of calcium in the coronary arteries. Purportedly, the

presence of (CAC) has been shown to be strongly correlated

with the extent of atherosclerotic plaque as well as the severity

of CAD. Tests to determine CAC scoring include multi-slice

computed tomography, and electron beam computed

tomography (EBCT), also known as ultrafast computed

tomography (UFCT).

Ultrafast computed tomography (also known as electron-beam

computed tomography [EBCT]) has been shown to be able to

quantify the amount of calcium in the coronary arteries, and

thus has been primarily investigated as a tool to predict risk of

CAD. In ultrafastCT, an electron-beam is magnetically

steered along stationary tungsten rings to produce a rotating X-

ray beam.

Research has indicated that EBCT is highly sensitive in

detecting coronary artery calcification in comparison to other

types of CT. Moreover, various studies have shown a strong

correlation between EBCT calcium scores and quantities of

atherosclerotic plaque. However, there is skepticism about the

relationship between EBCT calcium scores and the likelihood

of coronary events because of the following factors:

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▪ Calcium does not collect exclusively at sites with severe

stenosis

▪ EBCT calcium scores do not identify the location of specific

vulnerable lesions

▪ Substantial non-calcified plaque is frequently present in the

absence of coronary artery calcification

▪ There are no proven relationships between coronary

artery calcification and the probability of plaque

rupture.

Some advocates have argued that EBCT scores could be an

effective substitute for standard risk factors in predicting the

risk of coronary artery disease. However, citing evidence that

shows that only a small proportion of asymptomatic individuals

with calcified coronary arteries ultimately develop symptomatic

coronary artery disease, a 1996 American Heart Association

(AHA) scientific statement on coronary artery calcification

concludes that the presence of coronary artery calcium is a

poor predictor of coronary artery disease risk, and that there is

no role for ultrafast CT as a general screening tool to detect

atherosclerosis in people who have no symptoms of the

disease and no risk factors. More importantly, although a

negative scan may mean a low probability of significant artery

blockage in asymptomatic people with or without a previous

cardiac event (e.g., myocardial infarction, bypass surgery,

angioplasty, etc.), an unstable or vulnerable plaque may go

undetected by ultrafast CT, and may rupture and cause

thrombosis and obstruction of the coronary artery. Detrano

(1999) demonstrated that the addition of EBCT data provided

no added value to the risk of coronary artery disease risk

determined by the Framingham and National Cholesterol

Education Program risk models.

Several investigators have examined the potential role of

ultrafast CT measurements of coronary artery calcium in ruling

out coronary artery disease in patients with atypical anginal

symptoms. The AHA report estimates that the negative

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predictive value of an ultrafast CT scan in these patients

ranges from 90 to 95 %, and suggests that a negative study

may be useful in determining the need for further work-up with

exercise stress testing and/or angiography. It must be

realized, however, that ultrafast CT provides only anatomic

and not physiologic information. Although ultrafast CT can be

used to determine whether calcium is present in the coronary

arteries, it can not replace stress testing and angiography in

determining whether lesions result in significant coronary

artery obstruction and ischemia. Ultrafast CT is being

investigated for this proposed use.

The AHA does not recommend ultrafast CT as a replacement

for stress testing and/or angiography in patients with

conventional risk factors and in patients with typical anginal

chest pain. The increased predictive value of ultrafast CT of

the coronary arteries relative to traditional risk factor

assessment is not yet defined. Although a greater amount of

calcium may indicate a greater likelihood of obstructive

disease, studies have shown that site-specificity and exact 1:1

correlations are not well predicted, that is, ultrafast CT can not

define the location or amount of obstruction with sufficient

accuracy to be of use in predicting risk of coronary artery

disease, in diagnosing coronary artery disease, or in planning

surgical treatment.

Several studies have shown a variability in repeated measures

of coronary calcium by ultrafast CT; therefore, use of serial

ultrafast CT scans in individual patients to track the

progression or regression of calcium is problematic. Although

there is emerging evidence that ultrafast CT may help in

identifying the presence of early coronary artery disease in

people with known heart disease risk factors, there is no

definitive evidence that ultrafast CT can substitute for coronary

angiography because the absence of calcific deposits on an

ultrafast CT scan does not imply the absence of

atherosclerosis. Conversely, the presence of calcium does not

secure a diagnosis of significant angiographic narrowing.

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There is still a need for further clarification regarding the

relationship between calcification, atherosclerosis, and risk of

plaque rupture.

The critical issue that defines the utility (or lack thereof) of

ultrafast CT is its prognostic value. The evidence in the peer-

reviewed medical literature linking detectable coronary calcium

to event outcomes such as future coronary bypass surgery,

angioplasty, myocardial infarction, and coronary death is

limited. Large-scale prospective studies are still needed to

define a role for ultrafast CT.

In a review on coronary artery calcium scoring by m eans

of EBCT, Thomson and Hachamovitch (2002) stated that

studies have indicated that the very early detection of a

coronary artery burden is possible with EBCT. However, both

the Prevention Conference V and the ACC/AHA Expert

Consensus Document on EBCT have recommended against

the routine use of EBCT for screening for CAD in

asymptomatic individuals. Moreover, there is no evidence so

far to support using the results of EBCT in an asymptomatic

patient to select a therapy or to guide referral to invasive

investigations. The clinical role of EBCT is yet to be

established in terms of screening for disease or risk

assessment. Electron beam computed tomography is highly

sensitive, but its specificity is low. In fact, when referral to

angiography is based on the results of EBCT, referrals will be

made for very few patients with normal results while many

referrals will be made for those with abnormal results. The

outcome will be that, in clinical practice, the observed

sensitivity of EBCT will be increased, and the observed

specificity will be reduced. To date, there are no well-

conducted studies that clearly demonstrate the incremental

value of calcium scoring over traditional assessments of risk

factors, and the clinical role of EBCT is yet to be established in

terms of screening for disease or risk assessment. The

authors’ view is shared by Redberg and Shaw (2002) who

stated that widespread use of EBCT is not recommended.

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More research is needed to establish the effectiveness of

EBCT in the role of risk factor reduction and prevention of

cardiovascular disease. Furthermore, Greenland (2003)

stated that "To date, most research on EBT [electron-beam

computed tomography] has been observational in nature,

based entirely on self-referred patients" and that the "role of

EBT remains uncertain" and that "additional randomized trials

to define specific roles for EBT in risk prediction" are needed.

These conclusions are consistent with those of the U.S.

Preventive Services Task Force (2004), which stated that

there is "insufficient evidence to recommend for or against

routine screening with ... EBCT [electron beam CT] scanning

for coronary calcium for either the presence of severe

[coronary artery stenosis] or the prediction of [coronary heart

disease] events in adults at increased risk for coronary heart

disease.” The USPSTF reaffirmed their position in 2009,

stating that the evidence is insufficient to assess the balance

of benefits and harms of using coronary artery calcification

(CAC) score on electron-beam computed tomography (EBCT)

to screen asymptomatic men and women with no history of

CHD to prevent CHD events.

Guidelines from the American College of Cardiology and the

American Heart Association on assessment of cardiovascular

risk (Goff et al, 2014) concluded that CAC score may be

considered to inform decision making if, after quantitative risk

assessment, a risk-based treatment decision is uncertain. This

was a grade E recommendation (expert opinion), meaning

that “[t]here is insufficientevidence or evidence is unclear or

conflicting, but this is what the Work Group recommends.” The

guidelines state that, on the basis of current evidence, it is the

Work Group's opinion that assessments of CAC “show some

promise for clinical utility among the novel risk markers, based

on limited data.” The Work Group noted that a review by

Peters et al. (2012) provides evidence to support the

contention that assessing CAC is likely to be the most useful of

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the current approaches to improving risk assessment among

individuals found to be at intermediate risk after formal risk

assessment. Further research is recommended in this area.

American College of Cardiology/American Heart Association

guidelines (Greenland et al, 2010) have two Class

IIa recommendations for screening with calcium

scoring, where Class IIa recommendations are defined as

those for which “[t]he weight of evidence or opinion is in favor

of the procedure or treatment.” Class IIa recommendations for

calcium scoring are for asymptomatic patients with an

intermediate (10% to 20%) 10-year risk of cardiac events

based on the Framingham risk score (FRS) or other global risk

algorithm, and for asymptomatic patients 40 years and older

with diabetes mellitus. The guidelines state that there are no

data demonstrating that serial CAC testing leads to improved

outcomes or changes in therapeutic decision making.

Multi-slice (or multi-row detector) CT and spiral (or helical) CT

has also been used to quantify calcium in the coronary

arteries. Spiral or helical CT differs from conventional CT in

that the patient is continuously rotated as he is moved. Multi-

slice CT is a technical advance over spiral CT, and uses

multiple rows of detector arrays to rapidly obtain multiple slices

with one pass. Multi-slice CT differs from ultrafast CT in that

the latter has no moving parts, and ultrafast CT scans are

faster than with multi-sclice CT. One study examined the

accuracy of spiral CT in evaluating coronary calcification, using

ultrafast CT as the gold standard for comparison, in 33

asymptomatic individuals who were referred for calcium

scans. Spiral CT was reported to have a sensitivity of 74 %

and a specificity of 70 % compared to ultrafast CT. An

assessment of spiral CT and multi-slice CT in screening

persons with coronary artery disease by the Canadian

Coordinating Office for Health Technology Assessment (2003)

found no adequate long-term studies on clinical outcomes of

people screened with multi-slice CT or spiral CT. In addition,

the assessment failed to identify studies that compared spiral

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CT and multi-slice CT with established screening modalities

like risk factor algorithms. The authors noted that the low

specificity of spiral CT and multi-slice CT gives rise to concern

over false-positive results, and that false-positives may cause

harm and expense due to inappropriate and invasive follow-

up. The assessmentconcluded that “[t]here is insufficient

evidence at this time to suggest that asymptomatic people

derive clinical benefit from undergoing coronary calcification

screening using MSCT [multislice CT] or spiral CT scanning."

In an editorial accompanying a meta-analysis of electron-beam

CT for CAD by Pletcher et al (2004), Ewy (2004) explained

that "the clinical utility of fast computed tomography (CT)

scanners (i.e., the electron beam [EB] and double helical CT

scanner) is still limited. Electron beam CT is not ready for

prime time."

An assessment of the literature on calcium scoring by the

German Agency for Health Technology Assessment (DAHTA,

2006) concluded that measuring coronary calcium is a

"promising" tool for risk stratification, but that many questions

remain unanswered about the targeted use in medical

practice, including which patient groups should be screened,

which calcium score threshold should be applied, and which

scoring method should be used.

An assessment prepared for the National Coordinating Centre

for Health Technology Assessment (Waugh et al, 2006) found:

"CT examination of the coronary arteries can detect

calcification indicative of arterial disease in asymptomatic

people, many of whom would be at low risk when assessed by

traditional risk factors. The higher the CAC score, the higher

the risk. Treatment with statins can reduce that risk.

However, CT screening would miss many of the most

dangerous patches of arterial disease, because they are not

yet calcified, and so there would be false-negative results:

normal CT followed by a heart attack. There would also be

false-positive results in that many calcified arteries will have

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normal blood flow and will not be affected by clinically

apparent thrombosis: abnormal CT not followed by a heart

attack." The NCCHTA assessment concluded: "For CT

screening to be cost-effective, it has to add value over risk

factor scoring, by producing sufficient extra information to

change treatment and hence cardiac outcomes, at an

affordable cost per quality-adjusted life-year. There was

insufficient evidence to support this. Most of the NSC [National

Screening Committee] criteria were either not met or only

partially met."

An assessment by the Institute for Clinical Effectiveness and

Health Policy (Bardach, 2005) concluded: "Most consensus

consider EBCT, SCT and MSCT still at their investigational

stage for the following: (i) Detection of coronary artery

calcifications as a screening method for asymptomatic

subjects with coronary disease; (ii) Detection of coronary

artery calcifications in symptomatic patients; and (iii)

Assessment of coronary graft viability. No study reported

that calcification measuring (plaquecharacterization) reduces

the incidence of coronary events or death."

Detrano and associates (2008) noted that in white populations,

computed tomographic measurements of coronary artery

calcium (CAC) predict coronary heart disease

(CHD) independently of traditional coronary risk factors.

However, it is unclear if CAC predicts coronary heart disease

in other racial or ethnic groups. These researchers collected

data on risk factors and performed scanning for CAC in a

population-based sample of 6,722 men and women, of whom

38.6 % were white, 27.6 % were black, 21.9 % were Hispanic,

and 11.9 % were Chinese. The study subjects had no clinical

cardiovascular disease at entry and were followed for a

median of 3.8 years. There were 162 coronary events, of

which 89 were major events (myocardial infarction or death

from coronary heart disease). In comparison with participants

with no CAC, the adjusted risk of a coronary event was

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increased by a factor of 7.73 among participants with coronary

calcium scores between 101 and 300 and by a factor of 9.67

among participants with scores above 300 (p < 0.001 for both

comparisons). Among the 4 racial and ethnic groups, a

doubling of the calcium score increased the risk of a major

coronary event by 15 to 35 % and the risk of any coronary

event by 18 to 39 %. The AUCs for the prediction of both

major coronary events and any coronary event were higher

when the calcium score was added to the standard risk

factors. The authors concluded that the coronary calcium

score is a strong predictor of incident coronary heart disease

and provides predictive information beyond that provided by

standard risk factors in 4 major racial and ethnic groups in the

United States. No major differences among racial and ethnic

groups in the predictive value of calcium scores were

detected. While there were some interesting differences in the

prevalence of CAC among the 4 racial and ethnic groups, what

remains unclear is how this test should best be employed, or if

it should be used at all, to attain better health outcomes for

patients.

Calcium scoring may be useful when performed with an

otherwise indicated muti-slice cardiac CTA to assess the

calcium burden of the coronary arteries to determine whether

an adequate scan can be obtained. The calcium score may

be estimated with a scout scan, and the injection of contrast

withheld if it appears that the patienthas a prohibitively high

calcium score. This allows one to avoid exposing the patient

to unnecessary radiation from contrast if it is clear that the

patient's calcium score is so high that an adequate image of

the coronary vessels can not be obtained. In such cases, the

patient may need invasive angiography to adequately assess

the coronary vessels.

Baig and colleagues (2009) stated that CAD is present in 38

% to 40 % of patients starting dialysis. Both traditional and

chronic kidney disease-related cardiovascular risk factors

contribute to this high prevalence rate. In patients with end-

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stage renal disease, CAD, especially acute myocardial

infarction, is under-diagnosed. Dobutamine stress

echocardiography and, to a lesser extent, stress myocardial

perfusion imaging have proved useful in screening for CAD in

such patients. Coronary artery calcium scoring is less useful.

Acute myocardial infarction is associated with high short- and

long-term mortality in dialysis patients. Cardiac troponin I

appears to be more specific than cardiac troponin T or creatine

kinase MB subunits in the diagnosis of acute myocardial

infarction.

Ma and colleagues (2010) examined the relationship between

coronary calcium score (CCS) and angiographic stenosis on a

patient-based or vessel-based analysis. A total of 91

consecutive patients underwent both low-dose 64-slice CT

calcium scoring scan as well as conventional angiography of

the heart. The total CCS of abnormal coronary angiogram (n =

45) was 297.38 +/- 416.93, whereas that of normal coronary

angiogram (n = 46) was 5.37 +/- 9.35 (p < 0.001). The CCS

and degree of stenosis were moderately correlated on patient-

based or vessel-based analysis (r = 0.517, 0.521, respectively;

both p < 0.001). The authors concluded that CCS could reflect

the degree of vessel stenosis to some extent, but CCS of zero

could not rule out CAD.

Cademartiri et al (2010) compared the coronary artery calcium

score (CACS) and CTCA for the assessment of non-

obstructive/obstructive CAD in high-risk asymptomatic

subjects. A total of 213 consecutive asymptomatic subjects

(113 males; mean age of 53.6 +/- 12.4 years) with more than 1

risk factor and an inconclusive or unfeasible non-invasive

stress test result underwent CACS and CTCA in an out-patient

setting. All patients underwent conventional coronary

angiography (CAG). Data from CACS (threshold for positive

image: Agatston score 1/100/1,000) and CTCA were

compared with CAG regarding the degree of CAD (non-

obstructive/obstructive; less than/greater than or = 50 % lumen

reduction). The mean calcium score was 151 +/- 403 and the

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prevalence of obstructive CAD was 17 % (8 % 1-vessel and 10

% 2-vessel disease). Per-patient sensitivity, specificity,

positive and negative predictive values of CACS were: 97 %,

75 %, 45 %, and 100 %, respectively (Agatston greater than or

equal to 1); 73 %, 90 %, 60 %, and 94 %, respectively

(Agatston greater than or equal to 100); 30 %, 98 %, 79 %,

and 87 %, respectively (Agatston greater than or equal

to 1,000). Per-patient values for CTCA were 100 %, 98 %, 97

%, and 100 %, respectively (p < 0.05). Computed tomography

coronary angiography detected 65 % prevalence of all CAD

(48 % non-obstructive), while CACS detected 37 % prevalence

of all CAD (21 % non-obstructive) (p < 0.05). The authors

concluded that CACS proved inadequate for the detection of

obstructive and non-obstructive CAD compared with CTCA.

Computed tomography coronary angiography has a high

diagnostic accuracy for the detection of non-obstructive and

obstructive CAD in high-risk asymptomatic patients with

inconclusive or unfeasible stress test results.

Hadamitzky et al (2011) compared CCTA with calcium scoring

and clinical risk scores for the ability to predict cardiac events.

Patients (n = 2,223) with suspected CAD undergoing CCTA

were followed-up for a median of 28 months. The end point

was the occurrence of cardiac events (cardiac death, nonfatal

myocardial infarction, unstable angina requiring

hospitalization, and coronary re-vascularization later than 90

days after CCTA). Patients with obstructive CAD had a

significantly higher event rate (2.9 % per year; 95 % CI: 2.1 to

4.0) than those without obstructive CAD, having an event rate

0.3 % per year (95 % CI: 0.1 to 0.5; hazard ratio, 13.5; 95

% CI: 6.7 to 27.2; p < 0.001). Coronary computed tomography

angiography had significant incremental predictive value when

compared with calcium scoring, both with scores assessing the

degree of stenosis (p < 0.001) and with scores assessing the

number of diseased coronary segments (p = 0.027). The

authors concluded that in patients with suspected CAD, CCTA

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not only detects coronary stenosis but also improves

prediction of cardiac events over and above conventional risk

scores and calcium scoring.

In a prospective population-based study, Kavousi et al (2012)

evaluated if newer risk markers for CHD risk prediction and

stratification improve Framingham risk score (FRS)

predictions. A total of 5,933 asymptomatic, community-

dwelling participants (mean age of 69.1 years [SD, 8.5]) were

included in this analysis. Traditional CHD risk factors used in

the FRS (age, sex, systolic blood pressure, treatment of

hypertension, total and high-density lipoprotein cholesterol

levels, smoking, and diabetes) and newer CHD risk factors

(N-terminal fragment of prohormone B-type natriuretic peptide

levels, von Willebrand factor antigen levels, fibrinogen levels,

chronic kidney disease, leukocyte count, C-reactive protein

levels, homocysteine levels, uric acid levels, CACS, carotid

intima-media thickness, peripheral arterial disease, and pulse

wave velocity). Adding CACS to the FRS improved the

accuracy of risk predictions (c-statistic increase, 0.05 [95 % CI:

0.02 to 0.06]; net re-classification i ndex, 19.3 % overall [39.3

% in those at intermediate-risk, by FRS]). Levels of N-terminal

fragment of prohormone B-type natriuretic peptide also

improved risk predictions but to a lesser extent (c-statistic

increase, 0.02 [CI: 0.01 to 0.04]; net re-classification index, 7.6

% overall [33.0 % in those at intermediate-risk, by FRS]).

Improvements in predictions with other newer markers were

marginal. The authors concluded that among 12 CHD risk

markers, improvements in FRS predictions were most

statistically and clinically significant with the addition of CACS.

Moreover, they stated that further investigation is needed to

assess whether risk refinements using CACS lead to a

meaningful change i n clinical outcome.

Cho and colleagues (2012) stated that the predictive value of

CCTA in subjects without chest pain syndrome (CPS) has not

been established. These researchers investigated the

prognostic value of CAD detection by CCTA and determined

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the incremental risk stratification benefit of CCTA findings

compared with clinical risk factor scoring and CACS for

individuals without CPS. An open-label, 12-center, 6-country

observational registry of 27,125 consecutive patients

undergoing CCTA and CACS was queried, and 7,590

individuals without CPS or history of CAD met the inclusion

criteria. All-cause mortality and the composite of all-cause

mortality and non-fatal myocardial infarction were measured.

During a median follow-up of 24 months (interquartile range,

18 to 35 months), all-cause mortality occurred in 136

individuals. After risk adjustment, compared with individuals

without evidence of CAD by CCTA, individuals with obstructive

2- and 3-vessel disease or left main coronary artery disease

experienced higher rates of death and composite outcome (p <

0.05 for both). Both CACS and CCTA significantly improved

the performance of standard risk factor prediction models for all-

cause mortality and the composite outcome (likelihood ratio p <

0.05 for all), but the incremental discriminatory value associated

with their inclusion was more pronounced for the composite

outcome and for CACS (C statistic for model with risk factors

only was 0.71; for risk factors plus CACS, 0.75; for risk factors

plus CACS plus CCTA, 0.77). The net re- classification

improvement resulting from the addition of CCTA to a model

based on standard risk factors and CACS was negligible. The

authors concluded that although the prognosis for individuals

without CPS is stratified by CCTA, the additional risk-predictive

advantage by CCTA is not clinically meaningful compared with a

risk model based on CACS. Therefore, at present, the

application of CCTA for risk assessment of individuals without

CPS should not be justified.

The American College of Radiology Expert Panel on Cardiac

Imaging’s clinical guideline on “Chronic chest pain - low to

intermediate probability of coronary artery disease” (Woodard

et al, 2012) rendered a “3” rating for CT coronary calcium (a

“3” rating denotes the procedure is usually not appropriate).

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Dedic et al (2016) noted that it is uncertain whether a

diagnostic strategy supplemented by early CCTA is superior to

contemporary standard optimal care (SOC) encompassing high-

sensitivity troponin assays (hs-troponins) for patients suspected

of acute coronary syndrome (ACS) in the emergency

department (ED). In a prospective, open-label, multi-center,

randomized trial, these researchers examined if a diagnostic

strategy supplemented by early CCTA improves clinical

effectiveness compared with contemporary SOC. They enrolled

patients presenting with symptoms suggestive of an ACS at the

ED of 5 community and 2 university hospitals in the

Netherlands. Exclusion criteria included the need for urgent

cardiac catheterization and history of ACS or coronary re-

vascularization. The primary end-point was the number of

patients identified with significant CAD requiring re-

vascularization within 30 days. The study population

consisted of 500 patients, of whom 236 (47 %) were women

(mean age of 54 ± 10 years). There was no difference in the

primary end-point (22 [9 %] patients underwent coronary re-

vascularization within 30 days in the CCTA group and 17 [7 %]

in the SOC group [p = 0.40]). Discharge from the ED was not

more frequent after CCTA (65 % versus 59 %, p = 0.16), and

length of stay was similar (6.3 hours in both groups; p = 0.80).

The CCTA group had lower direct medical costs (€337 versus

€511, p < 0.01) and less outpatient testing after the index ED

visit (10 [4 %] versus 26 [10 %], p < 0.01).There was no

difference in incidence of undetected ACS. The authors

concluded that CCTA, applied early in the work-up of

suspected ACS, is safe and associated with less out-patient

testing and lower costs. However, they stated that in the era

of hs-troponins, CCTA did not identify more patients with

significant CAD requiring coronary re-vascularization, shorten

hospital stay, or allow for more direct discharge from the ED.

Calcium scores greater than 1000 have been taken as a

relative contraindication for CCTA (Maurya et al, 2016).

A calcium score of 1000 is often used as the cutoff value

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above which a CCTA will not be diagnostic (Lin, 2017).

Coronary CT Angiography for Assessment of Coronary Atherosclerosis in Asymptomatic Diabetics

Muhlestein and Moreno (2016) noted that it is well-known that

there is a very high risk of cardiovascular complications among

diabetic patients. In spite of all efforts at aggressive control of

diabetes and its complications, the incidence of cardiovascular

morbidity and mortality remains high, including in patients with

no prior symptoms, underscoring a possible advantage for

appropriate screening of asymptomatic patients for the

presence of obstructive CAD. These investigators reviewed

the results of studies designed to evaluate a possible role of

CCTA in the screening of asymptomatic diabetic patients for

possible obstructive CAD. The review of current literature

indicated that there is still no method of CAD screening

identified that has been shown to reduce the cardiovascular

risk of asymptomatic diabetic patients. Thus, the use and

value of screening for CAD in asymptomatic diabetic patients

remains controversial. CCTA screening has shown promise

and has been demonstrated to predict future risk, but as yet

has not demonstrated improvement in the outcomes of these

high-risk patients. At the present state of knowledge,

aggressive risk factor reduction appeared to be the most

important primary prevention strategy for all asymptomatic high-

risk diabetic patients. However, there remains a great need for

better and more sensitive and specific screening methods, as

well as more effective treatments that may allow clinicians to

more accurately target diabetic patients who really are at high

risk. The authors concluded that further large randomized and

well-controlled clinical trials are needed to examine if screening

for CAD could reduce cardiovascular event rates in patients

with diabetes.

Guaricci and colleagues (2018) stated that the prognostic

impact of diabetes mellitus (DM) on cardiovascular outcomes

is well known. As a consequence of previous studies showing

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the high incidence of CAD in diabetic patients and the

relatively poor outcome compared to non-diabetic populations,

DM is considered as CAD equivalent, which means that

diabetic patients are labeled as asymptomatic individuals at

high cardiovascular risk. Lessons learned from the analysis of

prognostic studies over the past decade have challenged this

dogma and now support the idea that diabetic population is not

uniformly distributed in the highest risk box. Detecting CAD in

asymptomatic high risk individuals is controversial and, what is

more, in patients with diabetes is challenging, and that is why

the reliability of traditional cardiac stress tests for detecting

myocardial ischemia is limited. The authors stated that CCTA

represents an emerging non-invasive technique able to

explore the atherosclerotic involvement of the coronary

arteries and, thus, to distinguish different risk categories

tailoring this evaluation on each patient.

Lee and associates (2018) noted that it is well-known that

diabetic patients have a high risk of cardiovascular events, and

although there has been a tremendous effort to reduce these

cardiovascular risks, the incidence of cardiovascular morbidity

and mortality in diabetic patients remains high. Thus, the early

detection of CAD is necessary in those diabetic patients who

are at risk of cardiovascular events. Significant medical and

radiological advancements, including CCTA, mean that it is

now possible to examine the characteristics of plaques,

instead of solely evaluating the calcium level of the coronary

artery. Recently, several studies reported that the prevalence

of subclinical coronary atherosclerosis (SCA) is higher than

expected, and this could impact on CAD progression in

asymptomatic diabetic patients. In addition, several reports

suggested the potential benefit of using CCTA for screening

for SCA in asymptomatic diabetic patients, which might

dramatically decrease the incidence of cardiovascular events.

For these reasons, the medical interest in SCA in diabetic

patients is increasing. The authors concluded that the

prevalence of SCA in diabetic patients is high, and the

progression of coronary atherosclerosis leads to the onset of

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future CV events and is associated with a poor prognosis.

Moreover, they stated that although CCTA screening has not

yet been demonstrated as improving the outcomes of

asymptomatic diabetic patients, it has been shown to be

beneficial in predicting future risk, and is promising for

screening with an additional technique.

Furthermore, an UpToDate review on “Screening for coronary

heart disease in patients with diabetes mellitus” (Bax et al,

2018) states that “In the 2018 Standards of Medical Care in

Diabetes, the American Diabetes Association does not

recommend routine screening for CHD in asymptomatic

patients with diabetes, as outcomes are not improved as long

as cardiovascular risk factors are treated. However, in the

2013 ESC/EASD Guidelines on diabetes, pre-diabetes, and

cardiovascular disease (CVD), the writing group concludes

that in asymptomatic patients routine screening is controversial

and still under debate. In addition, the guidelines highlight the

need for better definition of the characteristics of the patients

who should be screened for CHD, stating that screening for

silent myocardial ischemia may be considered in selected

high-risk patients with diabetes, such as patients with

peripheral artery disease or high coronary artery calcium

(CAC) score or with proteinuria”.

Appendix

Table 1 can be used to assess if a person has a low or very

low pre-test probability of CAD. Alternatively, pre-test

probability of CAD can be assessed using the Framingham

Risk Scoring Tool available at the following website, with low

risk defined as a 10-year risk of less than 10 %: Framingham

Risk Scoring Tool

(http://hp2010.nhlbihin.net/atpiii/calculator.asp?

usertype=prof). (For details on Framingham Risk Scoring, see

appendix to CPB 0381 - Cardiac Disease Risk Tests

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http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof

http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof


(../300_399/0381.html).) Or 10-year pretest probability

of atherosclerotic cardiovascular disease (ASCVD) can be

estimated using Pooled C ohort equations from

a downloadable spreadsheet and a web-based available at

Cardio Vascular Risk Calculator

(http://my.americanheart.org/cvriskcalculator) and Cardio

Vascular Prevention Guideline Tools

(http://www.cardiosource.org/science-and-quality/practice

guidelines-and-quality-standards/2013-prevention

guideline-tools.aspx).

Table 1: ACC Criteria for Pre-test Probability of CAD by Age,

Gender and Symptoms †

Age

(yrs)

Gender Typical /

Definite

Angina

Pectoris

Atypical /

Probable

Angina

Pectoris

Nonanginal

Chest Pain

Asymptomatic

Less

than

39

Men Intermediate Intermediate Low Very Low

Less

than

39

Women Intermediate Very Low Very Low Very Low

40-

49

Men High Intermediate Intermediate Low

40-

49

Women Intermediate Low Very Low Very Low

50-

59


50-

59

Women Intermediate Intermediate Low Very Low

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http://my.americanheart.org/cvriskcalculator

http://www.cardiosource.org/science-and-quality/practice-guidelines-and-quality-standards/2013-prevention-guideline-tools.aspx


60-

69


60-

69

Women High Intermediate Intermediate Low

Key:

▪ High: greater than 90 % pre-test probability

▪ Intermediate: between 10 % and 90 % pre-test

probability

▪ Low: between 5 % and 10 % pre-test probability

▪ Very low: less than 5 % pre-test probability

† No data exist for patients less than 30 years or greater than

69 years,but it can be assumed that prevalence of CAD

increases with age. In a few cases, patients with ages at the

extremes of the decades listed may have probabilities slightly

outside the high or low range.

Source: Adapted from Taylor et al., 2010

L ist 1: Clinical Classification of Chest Pain

Typical angina (definite):

(i) Substernal chest discomfort with a characteristic

quality and duration; and (ii) Provoked by exertion or

emotional stress; and (iii) Relieved by rest or

nitroglycerin

Atypical angina (probable):

Meets 2 of the above criteria.

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Non-cardiac chest pain:

Meets 1 or none of the above criteria.

Source: Snow et al, 2004.

L ist 2: Contraindications to Exercise Stress Testing

The following contraindications to exercise stress testing are

from the AHA/ACC guidelines:

▪ Acute aortic dissection

▪ Acute myocardial infarction (within 2 days)

▪ Acute myocarditis or pericarditis

▪ Acute pulmonary embolus or pulmonary infarction

▪ Symptomatic severe aortic stenosis

▪ Uncontrolled cardiac arrhythmias causing symptoms or

hemodynamic compromise

▪ Uncontrolled symptomatic heart failure

▪ Unstable angina not previously stabilized by medical

therapy.

In addition, exercise stress testing is not useful in persons who

are unable to exercise, persons on digoxin, persons who have

a cardiac conduction abnormality that prevents achievement of

an adequate heart rate response, persons on a medication

(e.g., beta blockers, other negative chronotropic agents) that

can not be stopped which prevent achievement of an

adequate heart rate response, and persons with an

uninterpretable electrocardiogram. The American College of

Cardiology defines an uninterpretable electrocardiogram as a

ventricular paced rhythm, complete left bundle branch block,

ventricular preexcitation arrhythmia (Wolfe Parkinson White

syndrome), or greater than 1 mm ST segment depression at

rest.

L ist 3: Contraindications to Pharmacological Stress

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Testing

The following are contraindications to adenosine or

dipyridamole (Persantine) stress testing:

▪ Active bronchospasm or reactive airway disease;

▪ Patients taking Persantine (contraindication to adenosine

stress testing);

▪ Patients using methylxanthines (e.g., caffeine and

aminophylline) (In general, patients should refrain from

ingesting caffeine for at least 24 hours prior to adenosineor

dipyridamole administration);

▪ Severe bradycardia (heart rate less than 40 beats/min);

▪ Sick sinus syndrome or greater than than first-degree heart

block (in persons without a ventricular-demand

pacemaker);

▪ Systolic blood pressure less than 90 mm Hg.

The following are contraindications to dobutamine stress

testing:

▪ Atrial tachyarrhythmias with uncontrolled ventricular

response;

▪ History of ventricular tachycardia;

▪ Left bundle branch block;

▪ Recent (within the past week) myocardial infarction;

▪ Significant aortic stenosis or obstructive cardiomyopathy;

▪ Thoracic aortic aneurysm;

▪ Uncontrolled hypertension;

▪ Unstable angina.

CPT Codes / HCPCS Codes / ICD-10 Codes

Information in the [brackets] below has been added for clarification purposes. Codes requiring a 7th character are represented by "+":

Proprietary


Proprietary

Code Code Description

Cardiac computed tomography (CT) angiography:

CPT codes covered if selection criteria are met:

0501T -

0504T

Noninvasive estimated c oronary fractional flow

reserve (FFR) derived from coronary computed

tomography angiography data using

computation fluid dynamics physiologic

simulation s oftware analysis of functional data

to assess the severity of coronary artery

disease

75571 Computed tomography, heart, without contrast

material, with quantitative evaluation of

coronary calcium [not covered for serial or

repeat calcium scoring]

75572 Computed tomography, heart, with contrast

material, for evaluation of cardiac structure and

morphology (including 3D image

postprocessing, assessment of cardiac

function, and evaluation of venous structure, if

performed

75573 Computed tomography, heart, with contrast

material, for evaluation of cardiac structure and

morphology in the setting of congenital heart

disease (including 3D image postprocessing,

assessment of LV cardiac function, RV

structure and function and evaluation of venous

structures, if performed

75574 Computed tomographic angiography, heart,

coronary arteries and bypass grafts (when

present), with contrast material, including 3D

image postprocessing (including evaluation of

cardiac structure and morphology, assessment

of cardiac function, and evaluation of venous

structures, if performed



Other CPT codes related to the CPB:

33250 -

33266

Cardiac tissue ablation procedures

33361 -

33369

Transcatheter aortic valve replacement with

prosthetic valve (TAVR/TAVI)

93015 -

93024

Cardiovascular stress testing and ergonovine

provocation test

93650 -

93657

Intracardiac catheter ablation procedures

ICD-10 codes covered if selection criteria is met (not all- inclusive):

E08.59 Diabetes mellitus due to underlying condition

with other circulatory complications [coronary

atherosclerosis in symptomatic diabetics]

E09.59 Drug or chemical induced diabetes mellitus with

other circulatory complications [coronary


E10.59 Type 1 diabetes mellitus with other circulatory

complications [coronary atherosclerosis in

symptomatic diabetics]

E11.59 Type 2 diabetes mellitus with other circulatory

complications [coronary atherosclerosis in

symptomatic diabetics]

E13.59 Other specified diabetes mellitus with other

circulatory complications [coronary


Proprietary



I06.0.

I 06.2

Rheumatic aortic stenosis and rheumatic aortic

stenosis with insufficiency [in the setting of

persons with suspected paradoxical low-flow,

low-gradient symptomatic severe aortic

stenosis when transthoracic echocardiography

is inconclusive]

I08.0,

I08.2,

I08.3

Rheumatic disorders of both mitral and aortic

valves, rheumatic disorders of both aortic and

tricuspid valves, & combined r heumatic

disorders of mitral, aortic and tricuspid valves

[in the setting of persons with suspected

paradoxical low-flow, low-gradient symptomatic

severe aortic stenosis when transthoracic

echocardiography is inconclusive]

I25.10 -

I25.119

Atherosclerotic heart disease of native coronary

artery

I25.700 -

I25.84

Atherosclerosis of coronary bypass graft(s) and

coronary artery of transplanted heart,

atherosclerosis of nonautologous biological

coronary bypass graft(s), chronic total occlusion

of coronary artery, coronary atherosclerosis due

to lipid rich plaque, and coronary

atherosclerosis due to calcified coronary

lesions

I35.0,

I35.2

Nonrheumatic aortic (valve) stenosis and

nonrheumatic aortic (valve) stenosis with

insufficiency [in the setting of persons with

suspected paradoxical low-flow, low-gradient

symptomatic severe aortic stenosis when

transthoracic echocardiography is inconclusive]

I37.0 -

I 37.9

Nonrheumatic pulmonary valve disorders

[pulmonary outflow obstruction]

Proprietary



I44.4 Left anterior fascicular block

I44.7 Left bundle-branch block, unspecified

I45.10 -

I45.19

Other and unspecified right bundle-branch

block

I48.0,

I48.1,

I48.2,

I48.91

Paroxysmal atrial fibrillation, persistent atrial

fibrillation, chronic atrial fibrillation, and

unspecified atrial fibrillation info [when rate-

controlled and 3rd generation D ual-Source CT

(DSCT) 120-kv tube voltage is utilized]

M30.3 Mucocutaneous lymph node syndrome

[Kawasaki disease]

Q21.1 Atria septal defect [aortic erosion in

symptomatic members (e.g., chest pain) who

have been treated for atrial septal defect with

an occlusive device]

Q21.3 Tetrology of Fallot

Q23.0 Congenital stenosis of aortic valve [in the

setting of persons with suspected paradoxical

low-flow, low-gradient symptomatic severe

aortic stenosis when transthoracic

echocardiography is inconclusive]

Q26.0 -

Q26.9

Congenital malformations of great veins

Q87.40 -

Q87.43

Marfan syndrome

R07.1 -

R07.9

Chest pain

Proprietary



R94.39 Abnormal result of other cardiovascular function

study [covered for evaluation of asymptomatic

persons at an intermediate pre-test probability

of coronary heart disease by Framingham risk

scoring (see Appendix) who have an equivocal

or uninterpretable exercise or pharmacological

stress test]

T82.01A -

T82.9xxS

Complications of cardiac and vascular

prosthetic devices, implants and grafts [when

echocardiographic imaging is inconclusive or

there is suspicion for paravalvular abscess

formation]

Z01.810 Encounter for preprocedural cardiovascular

examination [pre-operative assessment for

planned non- coronary cardiac surgeries]

Z68.41 -

Z68.45

Body mass index (BMI) 40.0 or greater [when

3rd generation DSCT 120-kv tube voltage is

utilized]

ICD-10 codes not covered for indications listed in the CPB ( no t all-inclusive):

C 38.0 Malignant neoplasm of heart [atrial

angiosarcoma]

ICD-10 codes contraindicated for this CPB (not all-inclusive):

I46.2 -

I 46.9

Cardiac arrest

I47.0

I47.9

I49.2

I49.3

Paroxysmal supraventricular tachycardia,

paroxysmal ventricular tachycardia, paroxysmal

tachycardia, unspecified

Proprietary



I48.1,

I48.3

I48.4,

I48.92

Atrial flutter

Z68.41 -

Z68.45

Body mass index 40 and over, adult

Z91.041 Radiographic dye allergy status [iodinated

contrast material]

Calcium Scoring:

HCPCS codes covered for indications listed in the CPB:

S8092 Electron beam computed tomography (also

known as ultrafast CT, cine CT)

ICD-10 codes covered if selection criteria is met (not all- inclusive):

E08.00 -

E 09.9

Diabetes mellitus due to underlying condition

[asymptomatic persons age 40 years and older]

E10.10 -

E 13.9

Diabetes mellitus [asymptomatic persons age

40 years and older]

Z13.6 Encounter for screening for cardiovascular

disorders

The above policy is based on the following references:

1. Wexler L, Brundage B, Crouse J, et al. Coronary artery

calcification: Pathophysiology, epidemiology, imaging

methods, and clinical implications. A statement for health

professionals from the American Heart Association

Writing Group. Circulation. 1996;94:1175-1192.

Proprietary


2. Marwick TH. Screening for coronary artery disease. Med

Clin North Am. 1999; 83(6):1375-1402.

3. Laudon DA. Use of electron-beam computed tomography

in the evaluation of chest pain patients in the emergency

department. Ann Emerg Med. 1999;33(1):15-21.

4. O'Malley PG. Rationale and design of the Prospective

Army Coronary Calcium (PACC) Study: Utility of electron

beam computed tomography as a screening test for

coronary artery disease and as an intervention for risk

factor modification among young, asymptomatic, active-

duty United States Army Personnel. Am Heart J.

1999;137(5):932-941.

5. Secci A, Wong N, Tang W, et al. Electron beam

computed tomography coronary calcium as a predictor of

coronary events. Circulation. 1997;96:1122-1129.

6. Rumberger JA, Sheedy PF, Breen JF, et al. Electron

beam computed tomography and coronary artery

disease: Scanning for coronary artery calcification. Mayo

Clin Proc. 1996;71:369-377.

7. Budoff MJ, Georgiou D, Brody A, et al. Ultrafast

computed tomography as a diagnostic modality in the

detection of coronary artery disease: A multicenter study.

Circulation. 1996;93:898-904.

8. Fallavollita JA, Brody AS, Bunnell IL, et al. Fast

computed tomography detection of coronary calcification

in the diagnosis of coronary artery disease: Comparison

with angiography in patients < 50 years old. Circulation.

1994;89(1):285-290.

9. Kaufmann RB, Peyser PA, Sheedy PF, et al.

Quantification of coronary artery calcium by electron

beam computed tomography for determination of severity

of angiographic disease in younger patients. J Am Coll

Cardiol. 1995;25:626-632.

10. Guerci AD, Spadaro LA, Popma JJ, et al. Relation of

coronary calcium score by electron beam computed

tomography to arteriography findings in asymptomatic

and symptomatic adults. Am J Cardiol. 1997;79:128-133.

Proprietary


11. Mann JM, Davies MJ. Vulnerable plaque: Relation of

characteristics to degree of stenosis in human coronary

arteries. Circulation. 1996;94:928-931.

12. Detrano R, Hsiai T, Wang S, et al. Prognostic value of

coronary calcification and angiographic stenoses in

patients undergoing coronary angiography. J Am Coll

Cardiol. 1996;27:285-290.

13. Arad Y, Spadaro LA, Goodman K, et al. Predictive value

of electron beam computed tomography of the coronary

arteries: 19-month follow-up of 1173 asymptomatic

subjects. Circulation. 1996;93:1951-1953.

14. Breen JF, Sheedy PF, Shwartz RS, et al. Coronary artery

calcification detected with ultrafast CT as an indication of

coronary artery disease. Radiology. 1992;185:435-439.

15. Committee on Advanced Cardiac Imaging and

Technology, Council on Clinical Cardiology, and

Committee on Newer Imaging Modalities, Council on

Cardiovascular Radiology, American Heart Association.

Potential value of ultrafast computed tomography to

screen for coronary artery disease. Circulation. 1993;87

(6):2071.

16. Wong ND, Detrano RC, Diamond G, et al. Does coronary

artery screening by electron beam computed tomography

motivate potentially beneficial lifestyle behaviors? Am J

Cardiol. 1996;78:1220-1223.

17. Wang S, Detrano RC, Secci A, et al. Detection of

coronary calcification with electron beam computed

tomography: Evaluation of interexamination

reproducibility and comparison of 3 image acquisition

protocols. Am Heart J. 1996;132:550-558.

18. Rumberger JA, Sheedy PF, Breen JF, et al. Electron

beam computed tomographic coronary calcium score cut

points and severity of associated angiographic lumen

stenosis. J Am Coll Cardiol. 1997;29:1542-1548.

19. Agatston AS, Janowitz WR, Hildner FJ, et al.

Quantification of coronary artery calcium using ultrafast

Proprietary


computed tomography. J Am Coll Cardiol. 1990;15:827-

832.

20. Berry E, Kelly S, Hutton J, et al. A systematic literature

review of spiral and electron beam computed

tomography: With particular reference to clinical

applications in hepatic lesions, pulmonary embolus, and

coronary artery disease. Health Technol Assess. 1999;3

(18):i-iv, 1-118.

21. Bielak LF, Rumberger JA, Sheedy PF 2nd, et al.

Probabilistic model for predication of angiographically

defined obstructive coronary artery disease using

electron beam computed tomography Calcium Score

Strata. Circulation. 2000;102(4):380-385.

22. Carr JJ, Crouse JR 3rd, Goff DC Jr, et al. Evaluation of

subsecond gated spiral CT for quantification of coronary

artery calcium and comparison with electron beam CT.

AJR Am J Roentgenol. 2000;174(4):915-921.

23. Detrano R, Wong ND, Doherty TM, et al. Coronary

calcium does not accurately predict near-term future

coronary events in high-risk adults. Circulation. 1999;99

(20):2633-2638.

24. O’Rourke RA, Brundage BH, Froelicher VF, et al.

American College of Cardiology/American Heart

Association expert consensus document on electron-

beam computed tomography for the diagnosis and

prognosis of coronary artery disease. J Am Coll Cardiol.

2000;36(1):326-340.

25. Ratko T. Electron beam computed tomography.

Technology Report. UHC Clinical Practice Advancement

Center.Oak Brook, IL: University Hospital Consortium

(UHC); October 1999.

26. Rumberger JA. Tomographic (plaque) imaging: State of

the art. Am J Cardiol. 2001;88(2-A):66E-69E.

27. Naghavi M, Madjid M, Khan MR, et al. New

developments in the detection of vulnerable plaque. Curr

Atheroscler Rep. 2001;3(2):125-135.

Proprietary


28. National Horizon Scanning Centre (NHSC). Imaging in

coronary heart disease - horizon scanning review.

Birmingham, UK: National Horizon Scanning Centre

(NHSC); 2001.

29. Redberg RF, Shaw LJ. A review of electron beam

computed tomography: Implications for coronary artery

disease screening. Prev Cardiol. 2002;5(2):71-78.

30. Nieman K, van Geuns RJ, Wielopolski P, et

al. Noninvasive coronary imaging in the new millennium:

A comparison of computed tomography and magnetic

resonance techniques. Rev Cardiovasc Med. 2002;3

(2):77-84.

31. Thomson LE, Hachamovitch R. Coronary artery calcium

scoring using electron-beam computed tomography:

Where does this test fit into a clinical practice? Rev

Cardiovasc Med. 2002;3(3):121-128.

32. O'Malley PG, Feuerstein IM, Taylor AJ. Impact of electron

beam tomography, with or without case management, on

motivation, behavioral change, and cardiovascular risk

profile: A randomized controlled trial. JAMA. 2003;289

(17):2215-2223.

33. Greenland P. Improving risk of coronary heart

disease. JAMA. 2003;289:2270-2272.

34. New Zealand Health Technology Assessment (NZHTA).

What is the prognostic value of calcium scoring in

screening asymptomatic populations for cardiovascular

disease? Evidence Tables. Christchurch, NZ: NZHTA;

2003. Available at: http://nzhta.chmeds.ac.nz. Accessed

April 16, 2004.

35. Pwee KH. Multislice/spiral computed tomography for

screening for coronary artery disease. Issues in

Emerging Health Technologies. Issue 43. Ottawa, ON:

Canadian Coordinating Office for Health Technology

Assessment (CCOHTA); February 2003. Available at:

http://www.ccohta.ca/. Accessed March 23, 2004.

36. Budoff MJ, Mao S, Zalace CP, et al. Comparison of spiral

and electron beam tomography in the evaluation of

Proprietary

http://nzhta.chmeds.ac.nz

http://www.ccohta.ca/


coronary calcification in asymptomatic persons. Int J

Cardiol. 2001;77(2-3):181-188.

37. U.S. Preventive Services Task Force. Screening for

coronary heart disease. Report of the U.S. Preventive

Services Task Force. Rockville, MD: Agency for

Healthcare Research and Quality (AHRQ); February

2004. Available at:

http://www.ahrq.gov/clinic/uspstf/uspsacad.htm. Accessed

March 23, 2004.

38. No author listed. AHA will not endorse EBT to assess

heart attack risk [news]. Pharmaceutical Executive.

October 10, 2004. Available at

http://www.pharmexec.com. Accessed November 3,

2004.

39. Jacoby DS, Mohler III ER, Rader DJ. Noninvasive

atherosclerosis imaging for predicting cardiovascular

events and assessing therapeutic interventions. Curr

Atheroscler Rep. 2004;6(1):20-26.

40. Mazzone T. The role of electron beam computed

tomography for measuring coronary artery

atherosclerosis. Curr Diab Rep. 2004;4(1):20-25.

41. Traversi E, Bertoli G, Barazzoni G, et al. Non-invasive

coronary angiography with multislice computed

tomography. Technology, methods, preliminary

experience and prospects. Ital Heart J. 2004;5(2):89-98.

42. Schoepf UJ, Becker CR, Ohnesorge BM, Yucel EK. CT of

coronary artery disease. Radiology. 2004;232(1):18-37.

43. Pletcher MJ, Tice JA, Pignone M, Browner WS. Using the

coronary artery calcium score to predict coronary heart

disease events: A systematic review and meta-analysis.

Arch Intern Med. 2004;164(12):1285-1292.

44. Ewy GA. The search for the 'holy grail' of clinically

significant coronary atherosclerosis. Arch Intern Med.

2004;16412):1266-1268.

45. Finnish Medical Society Duodecim. Coronary heart

disease (CHD): Symptoms, diagnosis and treatment. In:

EBM Guidelines. Evidence-Based Medicine [CD-ROM].

Proprietary

http://www.ahrq.gov/clinic/uspstf/uspsacad.htm

http://www.pharmexec.com


Helsinki, Finland: Duodecim Medical Publications Ltd.;

September 14, 2004.

46. Finnish Medical Society Duodecim. Coronary

angiography and indications for CABG or angioplasty. In:

EBM Guidelines. Evidence-Based Medicine [CD-ROM].

Helsinki, Finland: Duodecim Medical Publications Ltd.;

September 14, 2004.

47. Finnish Medical Society Duodecim. Unstable angina

pectoris. In: EBM Guidelines. Evidence-Based Medicine

[CD-ROM]. Helsinki, Finland: Duodecim Medical

Publications Ltd.; September 14, 2004.

48. Finnish Medical Society Duodecim. Myocardial infarction.

In: EBM Guidelines. Evidence-Based Medicine [CD-

ROM]. Helsinki, Finland: Duodecim Medical Publications

Ltd.; September 13, 2004.

49. American College of Cardiology Foundation, American

Heart Association. ACC/AHA 2002 guideline update for

the management of patients with chronic stable angina: A

report of the American College of Cardiology/American

Heart Association Task Force on Practice Guidelines

(Committee to update the 1999 guidelines). Bethesda,

MD: American College of Cardiology Foundation; 2002.

50. Snow V, Barry P, Fihn SD, et al. Primary care

management of chronic stable angina and asymptomatic

suspected or known coronary artery disease: A clinical

practice guideline from the American College of

Physicians. Ann Intern Med. 2004;141(7):562-567.

51. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA

guidelines for the management of patients with ST-

elevation myocardial infarction. A report of the American

College of Cardiology/American Heart Association Task

Force on Practice Guidelines (Committee to revise the

1999 guidelines). Bethesda, MD: American College of

Cardiology, American Heart Association; 2004.

52. Gibbons RJ, Balady GJ, Beasley JW, et al. ACC/AHA

guidelines for exercise testing. A report of the

American College of Cardiology/American Heart

Proprietary


Association Task Force on Practice Guidelines

(Committee on Exercise Testing). J Am Coll Cardiol.

1997l 30(1):260-311.


Heart Association. ACC/AHA guidelines for the

management of patients with unstable angina and non

ST-segment elevation myocardial infarction. A report of

the American College of Cardiology/American Heart

Association Task Force on Practice Guidelines.

Bethesda, MD: American College of Cardiology

Foundation (ACCF); March 2002.

54. Medical Services Advisory Committee (MSAC).

Diagnostic and therapeutic modalities for coronary artery

disease. Horizon Scanning 003. Canberra, ACT: MSAC;

2003.

55. Institute for Clinical Systems Improvement (ICSI).

Electron-beam and helical computed tomography for

coronary artery disease. Technology Assessment No. 34.

Bloomington, MN: ICSI; 2004.

56. BlueCross BlueShield Association (BCBSA), Technology

Evaluation Center (TEC). Contrast-enhanced cardiac

computed tomographic angiography for coronary artery

evaluation. TEC Assessment Program. Chicago, IL:

BCBSA; May 2005;20(4).

57. Lauer M, Froelicher ES, Williams M, Kligfield P. Exercise

testing in asymptomatic adults: A statement for

professionals from the American Heart Association

Council on Clinical Cardiology, Subcommittee on

Exercise, Cardiac Rehabilitation, and Prevention.

Circulation. 2005;112(5):771-776.


Heart Association. ACC/AHA guideline update for

exercise testing. A report of the American College of

Cardiology/American Heart Association Task Force on

Practice Guidelines (Committee on Exercise Testing).

Bethesda, MD: American College of Cardiology

Foundation; 2002.

Proprietary


59. Schuijf JD, Bax JJ, Shaw LJ, et al. Meta-analysis of

comparative diagnostic performance of magnetic

resonance imaging and multislice computed tomography

for noninvasive coronary angiography. Am Heart J.

2006;151(2):404-411.

60. Ontario Ministry of Health and Long-Term Care, Medical

Advisory Secretariat (MAS). Multi-detector computed

tomography angiography for coronary artery disease.

Health Technology Literature Review. Toronto, ON: MAS;

April 2005.

61. National Health Service Quality Improvement Scotland

(NHS QIS). The use of multislice computed tomography

angiography (CTA) for the diagnosis of coronary artery

disease. Evidence Note 9. Glasgow, Scotland: NHS QIS;

June 2005.

62. Foerster V, Murtagh J, Lentle BC, et al. CT and MRI for

selected clinical disorders: A systematic review of clinical

systematic reviews. Technology Report No. 59. Ottawa,

ON: Canadian Coordinating Office for Health Technology

Assessment (CADTH); 2005.

63. Bardach A, Garcia Marti S, Lopez A, Glujovsky D.

Usefulness of multislice computed tomography (MSCT)

for coronary disease. Report IRR No. 49. Buenos Aires,

Argentina: Institute for Clinical Effectiveness and Health

Policy (IECS); 2005.

64. National Horizon Scanning Centre (NHSC). Computed

tomography angiography for the diagnosis and

management of coronary artery disease. Horizon

Scanning Technology Briefing. Birmingham, UK: NHSC;

December 2006.

65. Budoff MJ, Achenbach S, Blumenthal RS, et al.

Assessment of coronary artery disease by cardiac

computed tomography. A Scientific Statement from the

American Heart Association Committee on

Cardiovascular Imaging and Intervention, Council on

Cardiovascular Radiology and Intervention, and

Proprietary


Committee on Cardiac Imaging, Council on Clinical

Cardiology. Circulation. 2006;114:1761-1791.

66. German Agency of Health Technology Assessment

(DAHTA) at German Institute for Medical Documentation

and Information (DIMDI). Computed tomography for the

measurement of coronary calcification in asymptomatic

risk patients [summary]. Technology Assessment.

Cologne, Germany; DIMDI; 2006.

67. Adelaide Health Technology Assessment (AHTA).

Computed tomography coronary angiography. Horizon

Scanning Prioritising Summary - Volume 12. Adelaide,

SA: AHTA on behalf of National Horizon Scanning Unit

(HealthPACT and MSAC); 2006.

68. Waugh N, Black C, Walker S, et al. The effectiveness

and cost-effectiveness of computed tomography

screening for coronary artery disease: Systematic review.

Health Technol Assess. 2006;10(39):1-60.

69. Murtagh J, Foerster V, Warburton RN, et al. Clinical and

cost effectiveness of CT and MRI for selected clinical

disorders: Results of two systematic reviews. Technology

Overview No. 22. Ottawa, ON: Canadian Agency for

Drugs and Technologies in Health (CADTH); 2006.

70. Murtagh J, Warburton RN, Foerster V, et al. CT and MRI

for selected clinical disorders: A systematic review of

economic evaluations. Technology Report No. 68.

Ottawa, ON: Canadian Agency for Drugs and

Technologies in Health (CADTH); 2006.

71. Eagle KA, Berger PB, Calkins H, et al. ACC/AHA

guideline update for perioperative cardiovascular

evaluation for noncardiac surgery-executive summary: A

report of the American College of Cardiology/American

Heart Association Task Force on Practice Guidelines

(Committee to Update the 1996 Guidelines on

Perioperative Cardiovascular Evaluation for Noncardiac

Surgery). J Am Coll Cardiol. 2002;39:542-53.

72. Goldstein JA, Gallagher MJ, O'Neill WW, et al. A

randomized controlled trial of multi-slice coronary

Proprietary


computed tomography for evaluation of acute chest pain.

J Am Coll Cardiol. 2007;49(8):863-871.

73. Ivan M, Kreisz F, Merlin T, et al. Multi-slice computed

tomography coronary angiography in the visualization of

coronary arteries. Assessment Report. MSAC Application

1105. Canberra, ACT: MSAC; November 2007.

74. Mowatt G, Cummins E, Waugh N, et al. Systematic

review of the clinical effectiveness and cost-effectiveness

of 64-slice or higher computed tomography angiography

as an alternative to invasive coronary angiography in the

investigation of coronary artery disease. Health Technol

Assess. 2008;12(17):1-164.

75. Einstein AJ, Henzlova MJ, Rajagopalan S. Estimating risk

of cancer associated with radiation exposure from 64-

slice computed tomography coronary angiography.

JAMA. 2007;298(3):317-323.

76. Detrano R, Guerci AD, Carr JJ, et al. Coronary calcium

as a predictor of coronary events in four racial or e thn ic

groups. N Engl J Med. 2008;358(13):1336-1345.

77. Mowatt G, Cook JA, Hillis GS, et al. 64-Slice computed

tomography angiography in the diagnosis and

assessment of coronary artery disease: Systematic

review and meta-analysis. Heart. 2008;94(11):1386-

1393.

78. Miller JM, Rochitte CE, Dewey M, et al. Diagnostic

performance of coronary angiography by 64-row CT. N

Engl J Med. 2008;359(22):2324-2336.

79. Baig SZ, Coats WC, Aggarwal KB, Alpert MA. Assessing

cardiovascular disease in the dialysis patient. Adv Perit

Dial. 2009;25:147-154.

80. U.S. Preventive Services Task Force (USPSTF). Using

nontraditional risk factors in coronary heart disease risk

assessment. Recommendations of the U.S. Preventive

Services Task Force. Rockville, MD: Agency for

Healthcare Research and Quality (AHRQ); October 2009.

81. Machaalany J,Yam Y, Ruddy TD, et al. Potential clinical

and economic consequences of noncardiac incidental

Proprietary


findings on cardiac computed tomography. J Am Coll

Cardiol. 2009;54(16):1533-1541.

82. American College of Cardiology Foundation Task Force

on Expert Consensus Documents, Mark DB, Berman DS,

Budoff MJ, et al.

ACCF/ACR/AHA/NASCI/SAIP/SCAI/SCCT 2010 expert

consensus document on coronary computed tomographic

angiography: A report of the American College of

Cardiology Foundation Task Force on Expert Consensus

Documents. Circulation. 2010;121(22):2509-2543.

83. Ma ES, Yang ZG, Li Y, et al.Correlation of calcium

measurement with low dose 64-slice CT and

angiographic stenosis in patients with suspected

coronary artery disease. Int J Cardiol. 2010;140(2):249-

252.

84. Cademartiri F, Maffei E, Palumbo A, et al. Coronary

calcium score and computed tomography coronary

angiography in high-risk asymptomatic subjects:

Assessment of diagnostic accuracy and prevalence of

non-obstructive coronary artery disease. Eur Radiol.

2010;20(4):846-854.

85. Hadamitzky M, Distler R, Meyer T, et al. Prognostic value

of coronary computed tomographic angiography in

comparison with calcium scoring and clinical risk scores.

Circ Cardiovasc Imaging. 2011;4(1):16-23.


Evaluation Center (TEC). Coronary computed

tomographic angiography in the evaluation of patients

with acute chest pain. TEC Assessment Program.

Chicago, IL: BCBSA; November 2011;26(9).

87. Alsheikh-Ali AA,Kitsios GD, Balk EM, et al. The

vulnerable atherosclerotic plaque: Scope of the literature.

Ann Intern Med. 2010;153(6):387-395.

88. von Ballmoos MW, Haring B, Juillerat P, Alkadhi H. Meta-

analysis: Diagnostic performance of low-radiation-dose

coronary computed tomography angiography. Ann Intern

Med. 2011;154(6):413-420.

Proprietary


89. Arbab-Zadeh A,Miller JM, Rochitte CE, et al. Diagnostic

accuracy of computed tomography coronary angiography

according to pre-test probability of coronary artery

disease and severity of coronary arterial calcification the

CORE-64 (Coronary Artery Evaluation Using 64-Row

Multidetector Computed Tomography Angiography)

international multicenter study. J Am Coll Cardiol.

2012;59(4):379-387.

90. Nissen SE. Coronary computed tomography

angiography: The challenge of coronary calcium. J Am

Coll Cardiol. 2012;59(4):388-389.

91. Kavousi M, Elias-Smale S, Rutten JH, et al. Evaluation of

newer risk markers for coronary heart disease risk

classification: A cohort study. Ann Intern Med. 2012;156

(6):438-444.

92. Cho I, Chang HJ, Sung JM, et al; CONFIRM

Investigators. Coronary computed tomographic

angiography and risk of all-cause mortality and nonfatal

myocardial infarction in subjects without chest pain

syndrome from the CONFIRM Registry (coronary CT

angiography evaluation for clinical outcomes: An

international multicenter registry). Circulation. 2012;126

(3):304-313.

93. Woodard PK, White RD, Abbara S, et al; Expert Panel on

Cardiac Imaging. ACR Appropriateness Criteria chronic

chest pain - low to intermediate probability of coronary

artery disease [online publication]. Reston, VA: American

College of Radiology (ACR); 2012.

94. Gorenoi V, Schönermark MP, Hagen A. CT coronary

angiography vs. invasive coronary angiography in CHD.

GMS Health Technol Assess. 2012;8:Doc02.

95. Liew GY, Feneley MP, Worthley SG. Appropriate

indications for computed tomography coronary

angiography. Med J Aust. 2012;196(4):246-249.

96. Greenland P,Alpert JS, Beller GA, et al.; American

College of Cardiology Foundation, American Heart

Association. 2010 ACCF/AHA guideline for assessment

Proprietary


of cardiovascular risk in asymptomatic adults: A report of

the American College of Cardiology Foundation/American

Heart Association Task Force on Practice Guidelines. J

Am Coll Cardiol. 2010;56(25):e50-e103.

97. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013

ACC/AHA Guideline on the assessment of cardiovascular

risk: A report of the American College of

Cardiology/American Heart Association Task Force on

Practice Guidelines. Circulation. 2014;63(25 Pt B):2935-

2959.

98. Peters SA, den Ruijter HM, Bots ML, Moons KG.

Improvements in risk stratification for the occurrence of

cardiovascular disease by imaging subclinical

atherosclerosis: A systematic review. Heart.

2012;98:177-184.

99. Kherada N, Mehran R. Pursuit of perfection: Three-

dimensional CT angiographic “objective quantification” of

aortic valve structures for transcatheter aortic valve

implantation. Cathet Cardiovasc Intervent. 2013;81:160

–161.

100. Westwood M, Al M, Burgers L, et al. A systematic review

and economic evaluation of new-generation computed

tomography scanners for imaging in coronary artery

disease and congenital heart disease: Somatom

Definition Flash, Aquilion ONE, Brilliance iCT and

Discovery CT750 HD. Health Technol Assess. 2013;17

(9):1-243.

101. Kim KJ, Choi SI, Lee MS, et al. The prevalence and

characteristics of coronary atherosclerosis in

asymptomatic subjects classified as low risk based on

traditional risk stratification algorithm: Assessment with

coronary CT angiography. Heart. 2013;99(15):1113-

1117.

102. Dorr R, Kadalie CT, Franke WG, Gutberlet M. Hybrid

imaging in diagnostics and therapy of chronic myocardial

ischemia. Clinical value. Herz. 2013;38(4):367-375.

Proprietary


103.

Kang EJ, Kim SM, Choe YH, et al. Takayasu arteritis:

Assessment of coronary arterial abnormalities with 128-

section dual-source CT angiography of the coronary

arteries and aorta. Radiology. 2014;270(1):74-81.

104. Criqui MH, Denenberg JO, Ix JH, et al. Calcium density o f

coronary artery plaque and risk of incident cardiovascular

events. JAMA. 2014;311(3):271-278.

105. Jiang B, Wang J, Lv X, Cai W. Dual-source CT versus

single-source 64-section CT angiography for coronary

artery disease: A meta-analysis. Clin Radiol. 2014;69

(8):861-869.

106. Dedic A, Lubbers MM, Schaap J, et al. Coronary CT

angiography for suspected ACS in the era of high-

sensitivity troponins: Randomized multicenter study. J

Am Coll Cardiol. 2016;67(1):16-26.

107. Knapper JT, Khosa F, Blaha MJ, et al. Coronary calcium

scoring for long-term mortality prediction in patients with

and without a family history of coronary disease. Heart.

2016;102(3):204-208.

108. National Institute for Health and Care Excellence

(NICE). HeartFlow FFRCT for estimating fractional flow

reserve from coronary CT angiography. Medical

Technology Consultation Document. London, UK: NICE;

July 2016.


Evaluation Center (TEC). Fractional flow reserve and

coronary artery revascularization. TEC Assessment

Program. Chicago, IL: BCBSA; July 2011;26(2).

110. van den Hoogen IJ, de Graaf MA, Roos CJ, et al.

Prognostic value of coronary computed tomography

angiography in diabetic patients without chest pain

syndrome. J Nucl Cardiol. 2016;23(1):24-36.

111. Cantoni V, Green R, Acampa W, et al. Long-term

prognostic value of stress myocardial perfusion imaging

and coronary computed tomography angiography: A

meta-analysis. J Nucl Cardiol. 2016;23(2):185-197.

Proprietary


112.

Wu W, Pan DR, Foin N, et al. Noninvasive fractional flow

reserve derived from coronary computed tomography

angiography for identification of ischemic lesions: A

systematic review and meta-analysis. Sci Rep.

2016;6:29409

113. Baumann S, Renker M, Hetjens S, et al. Comparison of

coronary computed tomography angiography-derived vs

invasive fractional flow reserve assessment: Meta-

analysis with subgroup evaluation of intermediate

stenosis. Acad Radiol. 2016;23(11):1402-1411.

114. Opolski MP, Staruch AD, Jakubczyk M, et al. CT

angiography for the detection of coronary artery stenoses

in patients referred for cardiac valve surgery: Systematic

review and meta-analysis. JACC Cardiovasc Imaging.

2016;9(9):1059-1070.

115. Curzen NP, Nolan J, Zaman AG, et al. Does the routine

availability of CT-derived FFR influence management

of patients with stable chest pain compared to

CT angiography alone?: The FFR(CT) RIPCORD Study.

JACC Cardiovasc Imaging. 2016;9(10):1188-1194.

116. Douglas PS, De Bruyne B, Pontone G, et al.;

PLATFORM Investigators. 1-year outcomes of FFRCT-

guided care in patients with suspected coronary disease:

The PLATFORM Study. J Am Coll Cardiol. 2016;68

(5):435-445.

117. Nørgaard BL, Hjort J, Gaur S, et al. Clinical use of

coronary CTA-derived FFR for decision-making in stable

CAD. JACC Cardiovasc Imaging. 2017;10(5):541-550.

118. Douglas PS, Pontone G, Hlatky MA, et al.; PLATFORM

Investigators.. Clinical outcomes of fractional flow reserve

by computed tomographic angiography-guided diagnostic

strategies vs. usual care in patients with suspected

coronary artery disease: The prospective longitudinal trial

of FFR(CT): Outcome and resource impacts study. Eur

Heart J.

2015;36(47):3359-3367.

Proprietary


119.

Hlatky MA, De Bruyne B, Pontone G, et al.; PLATFORM

Investigators.. Quality-of-life and economic outcomes of

assessing fractional flow reserve with computed

tomography angiography: PLATFORM. J Am Coll

Cardiol. 2015;66(21):2315-2323.

120. Leipsic J, Yang TH, Thompson A, et al. CT angiography

(CTA) and diagnostic performance of noninvasive

fractional flow reserve: Results from the Determination of

Fractional Flow Reserve by Anatomic CTA (DeFACTO)

study. AJR Am J Roentgenol. 2014;202(5):989-994.

121. Nørgaard BL, Leipsic J, Gaur S, et al; NXT Trial

Study Group. Diagnostic performance of noninvasive

fractional flow reserve der ived from coronary computed

tomography angiography in suspected coronary artery

disease: The NXT trial (Analysis of Coronary Blood Flow

Using CT Angiography: Next Steps). J Am Coll Cardiol.

2014;63(12):1145-1155.

122. Min JK, Koo BK, Erglis A, et al. Effect of image quality on

diagnostic accuracy of noninvasive fractional flow

reserve: Results from the prospective multicenter

international DISCOVER-FLOW study. J Cardiovasc

Comput Tomogr. 2012;6(3):191-199.

123. National Institute for Health and Care Excellence (NICE).

HeartFlow FFRCT for estimating fractional flow reserve

from coronary CT angiography. Medical Technology

Guidance 32. London, UK: NICE; February 2017.

124. U.S. Food and Drug Administration (FDA). HeartFlow

FFRCT Coronary Physiologic Simulation Software

Device. 510(k) Summary. 510(k) No. K161772. Silver

Spring, MD: FDA; August 24, 2016.

125. Messenger JC, Moussa ID, Masoudi FA. Upcoming

changes and rationale in the NCDR CathPCI data

requirements. Expert Analysis. Washington, DC:

American College of Cardiology; January 23, 2017.

126. Chen MY, Shanbhag SM, Arai AE. Submillisievert

median radiation dose for coronary angiography with

a second-generation 320–detector row CT scanner in

Proprietary


107 consecutive patients. Radiology. 2013;267(1):76

85.

127.

Foy AJ, Dhruva SS, Peterson B, et al. Coronary

computed tomography angiography vs functional

stress testing for patients with suspected coronary

artery disease: A systematic review and meta-analysis.

JAMA Intern Med. 2017;177(11):1623-1631.

128. Tan XW, Zheng Q, Shi L, et al. Combined diagnostic

performance of coronary computed tomography

angiography and computed tomography derived

fractional flow reserve for the evaluation of myocardial

ischemia: A meta-analysis. Int J Cardiol. 2017;236:100

106.

129. Kishi S, Giannopoulos AA, Tang A, et al. Fractional flow

reserve estimated at coronary CT angiography in

intermediate lesions: Comparison of diagnostic

accuracy of different methods to determine coronary

flow distribution. Radiology. 2018;287(1):76-84.

130. Abbara S, Blanke P, Maroules CD, et al. SCCT

guidelines for the performance and acquisition of

coronary computed tomographic angiography: A

report of the society of Cardiovascular Computed

Tomography Guidelines Committee: Endorsed by the

North American Society for Cardiovascular Imaging

(NASCI). J Cardiovasc Comput Tomogr. 2016;10(6):435

449.

131. Fihn SD, Gardin JM, Abrams J, et al.; American College

of Cardiology Foundation.; American Heart Association

Task Force on Practice Guidelines.; American College

of Physicians.; American Association for Thoracic

Surgery.; Preventive Cardiovascular Nurses

Association.; Society for Cardiovascular Angiography

and Interventions.; Society of Thoracic Surgeons.. 2012

ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the

diagnosis and management of patients with stable

ischemic heart disease: a report of the American

College of Cardiology Foundation/American Heart

Proprietary


Association Task Force on Practice Guidelines, and the

American College of Physicians, American Association

for Thoracic Surgery, Preventive Cardiovascular Nurses

Association, Society for Cardiovascular Angiography

and Interventions, and Society of Thoracic Surgeons. J

Am Coll Cardiol. 2012;60(24):e44-e164.

132.

Fihn SD, Blankenship JC, Alexander KP, et al. 2014

ACC/AHA/AATS/PCNA/SCAI/STS focused update of the

guideline for the diagnosis and management of

patients with stable ischemic heart disease: a report of

the American College of Cardiology/American Heart

Association Task Force on Practice Guidelines, and the

American Association for Thoracic Surgery, Preventive

Cardiovascular Nurses Association, Society for

Cardiovascular Angiography and Interventions, and

Society of Thoracic Surgeons. J Am Coll Cardiol.

2014;64(18):1929-49.

133. Hoffmann U, Ferencik M, Udelson JE, et al; PROMISE

Investigators.. Prognostic value of noninvasive

cardiovascular testing in patients with stable chest

pain: Insights from the PROMISE trial (Prospective

Multicenter Imaging Study for Evaluation of Chest

Pain). Circulation. 2017;135(24):2320-2332.

134. Jørgensen ME, Andersson C, Nørgaard BL, et al.

Functional testing or coronary computed tomography

angiography in patients with stable coronary artery

disease. J Am Coll Cardiol. 2017;69(14):1761-1770.

135. Marwick TH, Cho I, Ó Hartaigh B, et al. Finding the

gatekeeper to the cardiac catheterization laboratory:

coronary CT angiography or stress testing? J Am Coll

Cardiol. 2015;65(25):2747-56.

136. Williams MC, Hunter A, Shah ASV, et al.; SCOT-HEART

Investigators.. Use of coronary computed tomographic

angiography to guide management of patients with

coronary disease. J Am Coll Cardiol. 2016;67(15):1759

1768.

Proprietary


137.

Williams MC, Moss A, Nicol E, et al. Cardiac CT

improves outcomes in stable coronary heart disease:

Results of recent clinical trials. Current Cardiovascular

Imaging Reports. 2017;10(5):14.

138. Lin EC. Coronary CT angiography. Medscape. 2017.

Available at:

https://emedicine.medscape.com/article/1603072

overview#showall. Accessed May 15, 2018.

139. Maurya VK, Ravikumar R, Sharma P, et al. Coronary CT

angiography: A retrospective study of 220 cases.

Medical Journal, Armed Forces India. 2016;72(4):377

383.

140. Ramjattan NA, Makaryus AN. Coronary CT

angiography. 2017. StatPearls [Internet]. Treasure

Island (FL): StatPearls Publishing; 2018 Jan-. Available

From

http://www.ncbi.nlm.nih.gov/books/NBK470279/.

Accessed May 16, 2018.

141. HeartFlow, Inc. HeartFlow announces its novel, non

invasive FFRct technology for coronary artery disease

receives positive review from Blue Cross Blue Shield.

Business Wire. Redwood, CA. June 2017. Available at:

https://www.businesswire.com/news/home/20170612005544/en/HeartFlow

Announces-Non-Invasive-FFRct-Technology-Coronary-

Artery. Accessed May 15, 2018.

142. Bluemke DA, Achenbach S, Budoff M, et al.

Noninvasive coronary artery imaging: magnetic

resonance angiography and multidetector computed

tomography angiography: A scientific statement from

the american heart association committee on

cardiovascular imaging and intervention of the council

on cardiovascular radiology and intervention, and the

councils on clinical cardiology and cardiovascular

disease in the young. Circulation. 2008;118(5):586-606.

143. Ollendorf DA, Kuba M, Pearson SD. The diagnostic

performance of multi-slice coronary computed

Proprietary

http://www.ncbi.nlm.nih.gov/books/NBK470279/

http://www.businesswire.com/news/home/20170612005544/en/HeartFlow-Announces-Non-Invasive-FFRct-Technology-Coronary-Artery


https://emedicine.medscape.com/article/1603072-overview#showall

https://emedicine.medscape.com/article/1603072-overview#showall



tomographic angiography: A systematic review. Journal

of General Internal Medicine. 2011;26(3):307-316.

144.

Lin FY, Shaw LJ, Dunning AM, et al. Mortality risk in

symptomatic patients with nonobstructive coronary

artery disease: a prospective 2-center study of 2,583

patients undergoing 64-detector row coronary

computed tomographic angiography. J Am Coll Cardiol.

2011;58(5):510-9.

145. SCOT-HEART investigators.. CT coronary angiography

in patients with suspected angina due to coronary

heart disease (SCOT-HEART): An open-label, parallel-

group, multicentre trial. Lancet. 2015;385(9985):2383

91.

146. Hulten E, Bittencourt MS, Singh A, et al. Coronary

artery disease detected by coronary computed

tomographic angiography is associated with

intensification of preventive medical therapy and

lower low-density lipoprotein cholesterol. Circ

Cardiovasc Imaging. 2014;7(4):629-38.

147. Hulten EA. Does FFRct have proven utility as a

gatekeeper prior to invasive angiography? J. Nucl.

Cardiol. 2017;24(5):1619-25.

148. Blaha MJ, Cainzos-Achirica M, Greenland P, et al. Role

of coronary artery calcium score of zero and other

negative risk markers for cardiovascular disease: The

Multi-Ethnic Study Of Atherosclerosis (MESA).

Circulation. 2016;133(9):849-858.

149. Bell DJ, Wichmann JL, et al. Cardiac CT. Radiopaedia.

Available at: https://radiopaedia.org/articles/cardiac

ct-1. Accessed May 18, 2018.

150. Soman P, Truong QA, Udelson JE. Noninvasive testing

and imaging for diagnosis in patients at low to

intermediate risk for acute coronary syndrome.

UpToDate [online serial]. Waltham, MA: UpToDate;

reviewed July 2017.

151. Yang L, Xu L, Schoepf UJ, et al. Prospectively ECG-

triggered sequential dual-source coronary CT

Proprietary

https://radiopaedia.org/articles/cardiac-ct-1

https://radiopaedia.org/articles/cardiac-ct-1


angiography in patients with atrial fibrillation:

Influence of heart rate on image quality and evaluation

of diagnostic accuracy. Zhang H, ed. PLoS ONE.

2015;10(7):e0134194.

152. Prazeres CEED, Magalhães TA, de Castro Carneiro

AC, et al. Image quality and radiation exposure

comparison of a double high-pitch acquisition for

coronary computed tomography angiography versus

standard retrospective spiral acquisition in patients

with atrial fibrillation. J Comput Assist Tomogr. 2018;42

(1):45-53.

153. Mangold S, Wichmann JL, Schoepf UJ, et al. Coronary

CT angiography in obese patients using 3(rd)

generation dual-source CT: effect of body mass index

on image quality. Eur Radiol. 2016;26(9):2937-46.

154. Chinnaiyan KM, McCullough PA, Flohr TG, et al.

Improved noninvasive coronary angiography in

morbidly obese patients with dual-source computed

tomography. J Cardiovasc Comput Tomogr. 2009;3

(1):35-42.

155. Taylor AJ, Cerqueira M, Hodgson JM, et al.; American

College of Cardiology Foundation Appropriate Use

Criteria Task Force.; Society of Cardiovascular

Computed Tomography.; American College of

Radiology.; American Heart Association.; American

Society of Echocardiography; American Society of

Nuclear Cardiology.; North American Society for

Cardiovascular Imaging.; Society for Cardiovascular

Angiography and Interventions.; Society for

Cardiovascular Magnetic Resonance..

ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR

2010 Appropriate Use Criteria for Cardiac Computed

Tomography. A Report of the American College of

Cardiology Foundation Appropriate Use Criteria Task

Force, the Society of Cardiovascular Computed

Tomography, the American College of Radiology, the

American Heart Association, the American Society of

Proprietary


Echocardiography, the American Society of Nuclear

Cardiology, the North American Society for

Cardiovascular Imaging, the Society for Cardiovascular

Angiography and Interventions, and the Society for

Cardiovascular Magnetic Resonance. J Cardiovasc

Comput Tomogr. 2010;4(6):407.e1-e33.

156.

Muhlestein JB, Moreno FL. Coronary computed

tomography angiography for screening in patients

with diabetes: Can enhanced detection of subclinical

coronary atherosclerosis improve outcome? Curr

Atheroscler Rep. 2016;18(11):64.

157. Guaricci AI, De Santis D, Carbone M, et al. Coronary

atherosclerosis assessment by coronary CT

angiography in asymptomatic diabetic population: A

critical systematic review of the literature and future

perspectives. Biomed Res Int. 2018;2018:8927281.

158. Lee CH, Lee SW, Park SW. Diabetes and subclinical

coronary atherosclerosis. Diabetes Metab J. 2018;42

(5):355-363.

159. Bax JJ, Wackers FJT, Delgado V. Screening for coronary

heart disease in patients with diabetes mellitus.

UpToDate Inc., Waltham, MA. Last reviewed November

2018.

160. National Institute for Health and Clinical Excellence

(NICE) . Chest pain of recent onset: Assessment and

diagnosis of recent onset chest pain or discomfort of

suspected cardiac origin (update). Clinical Guideline

95. London, UK: NICE; 2016.

161. Douglas PS, Hoffman U, Patel MR, et al. Outcomes of

anatomical versus functional testing for coronary

artery disease. N Engl J Med. 2015;372:1291-1300.

Proprietary


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AETNA BETTER HEALTH® OF PENNSYLVANIA

Amendment to Aetna Clinical Policy Bulletin Number: 0228 Cardiac CT,

Coronary CT Angiography, Calcium Scoring and CT Fractional Flow Reserve

There are no amendments for Medicaid.

www.aetnabetterhealth.com/pennsylvania annual 06/01/2020

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